|
|
|
Insulin: a small protein with a long journey |
| Qingxin Hua, |
| Department of Biochemistry,
Case Western Reserve University, Cleveland, Ohio 44106-4935, USA; |
|
|
|
|
Abstract Insulin is a hormone that is essential for regulating energy storage and glucose metabolism in the body. Insulin in liver, muscle, and fat tissues stimulates the cell to take up glucose from blood and store it as glycogen in liver and muscle. Failure of insulin control causes diabetes mellitus (DM). Insulin is the unique medicine to treat some forms of DM. The population of diabetics has dramatically increased over the past two decades, due to high absorption of carbohydrates (or fats and proteins), lack of physical exercise, and development of new diagnostic techniques. At present, the two largest developing countries (India and China) and the largest developed country (United States) represent the top three countries in terms of diabetic population. Insulin is a small protein, but contains almost all structural features typical of proteins: α-helix, β-sheet, β-turn, high order assembly, allosteric T®R-transition, and conformational changes in amyloidal fibrillation. More than ten years’ efforts on studying insulin disulfide intermediates by NMR have enabled us to decipher the whole picture of insulin folding coupled to disulfide pairing, especially at the initial stage that forms the nascent peptide. Two structural switches are also known to regulate insulin binding to receptors and progress has been made to identify the residues involved in binding. However, resolving the complex structure of insulin and its receptor remains a challenge in insulin research. Nevertheless, the accumulated knowledge of insulin structure has allowed us to specifically design a new ultra-stable and active single-chain insulin analog (SCI-57), and provides a novel way to design super-stable, fast-acting and cheaper insulin formulations for DM patients. Continuing this long journey of insulin study will benefit basic research in proteins and in pharmaceutical therapy.
|
| Keywords
insulin
diabetes
receptor binding
folding
disulfide pairing
NMR
|
|
Issue Date: 01 June 2010
|
|
|
Adams, T.E., Epa, V.C., Garrett, T.P.J., and Ward, C.W. (2000). Structure and function of the type 1 insulin-like growthfactor receptor. Cell Mol Life Sci57, 1050―1093.
doi: 10.1007/PL00000744
|
|
Ahmad, A., Millett, I.S., Doniach, S., Uversky, V.N., and Fink, A.L. (2003). Partiallyfolded intermediates in insulin fibrillation. Biochemistry42, 11404―11416.
doi: 10.1021/bi034868o
|
|
Anfinsen, C.B. (1973). Principles that govern the folding of protein chains. Science181, 223―230.
doi: 10.1126/science.181.4096.223
|
|
Badger, J., Harris, M.R., Reynolds, C.D., Evans, A.C., Dodson, E.J., Dodson, G.G., and North, A.C. (1991). Structure of the pig insulin dimer in the cubic crystal. Acta Crystallogr B47, 127―136.
doi: 10.1107/S0108768190009570
|
|
Baker, E.N., Blundell, T.L., Cutfield, J.F., Cutfield, S.M., Dodson, E.J., Dodson, G.G., Hodgkin, D.M., Hubbard, R.E., Isaacs, N.W., Reynolds, C.D., et al.(1988). The structure of 2Zn pig insulin crystalsat 1.5 A resolution. Philos Trans R SocLond B Biol Sci319, 369―456.
doi: 10.1098/rstb.1988.0058
|
|
Bao, S.J., Xie, D.L., Zhang, J.P., Chang, W.R., and Liang, D.C. (1997). Crystalstructure of desheptapeptide(B24―B30)insulinat 1.6 A resolution: implications for receptor binding. Proc Natl Acad Sci U S A94, 2975―2980.
doi: 10.1073/pnas.94.7.2975
|
|
Bentley, G., Dodson, E., Dodson, G., Hodgkin, D., and Mercola, D. (1976). Structureof insulin in 4-zinc insulin. Nature261, 166―168.
doi: 10.1038/261166a0
|
|
Blundell, T.L., Cutfield, J.F., Cutfield, S.M., Dodson, E.J., Dodson, G.G., Hodgkin, D.C., Mercola, D.A., and Vijayan, M. (1971). Atomicpositions in rhombohedral 2-zinc insulin crystals. Nature231, 506―511.
doi: 10.1038/231506a0
|
|
Brange, J. (1987). Galenics of insulin: the physico-chemical and pharmaceuticalaspects of insulin and insulin preparations (Berlin: Springer-Verlag).
|
|
Brange, J., Andersen, L., Laursen, E.D., Meyn, G., and Rasmussen, E. (1997a). Towardunderstanding insulin fibrillation. J PharmSci86, 517―525.
doi: 10.1021/js960297s
|
|
Brange, J., Dodson, G.G., Edwards, D.J., Holden, P.H., and Whittingham, J.L. (1997b). A modelof insulin fibrils derived from the x-ray crystal structure of a monomericinsulin (despentapeptide insulin). Proteins27, 507―516.
doi: 10.1002/(SICI)1097-0134(199704)27:4<507::AID-PROT4>3.0.CO;2-7
|
|
Brange, J., and Langkjaer, L. (1997). Insulinformulation and delivery. Pharm Biotechnol10, 343―409.
doi: 10.1007/0-306-46803-4_13
|
|
Bucciantini, M., Giannoni, E., Chiti, F., Baroni, F., Formigli, L., Zurdo, J., Taddei, N., Ramponi, G., Dobson, C.M., and Stefani, M. (2002). Inherent toxicity of aggregates implies a common mechanismfor protein misfolding diseases. Nature416, 507―511.
doi: 10.1038/416507a
|
|
Chothia, C., Lesk, A.M., Dodson, G.G., and Hodgkin, D.C. (1983). Transmission of conformational change in insulin. Nature302, 500―505.
doi: 10.1038/302500a0
|
|
Ciszak, E., and Smith, G.D. (1994). Crystallographicevidence for dual coordination around zinc in the T3R3 human insulinhexamer. Biochemistry33, 1512―1517.
doi: 10.1021/bi00172a030
|
|
Cohen, F.E. (1999). Protein misfolding and prion diseases. J Mol Biol293, 313―320.
doi: 10.1006/jmbi.1999.2990
|
|
Colombo, C., Porzio, O., Liu, M., Massa, O., Vasta, M., Salardi, S., Beccaria, L., Monciotti, C., Toni, S., Pedersen, O., et al.,and the Early Onset Diabetes Study Group of the Italian Society ofPediatric Endocrinology and Diabetes (SIEDP). (2008). Seven mutations in the human insulin gene linked to permanent neonatal/infancy-onsetdiabetes mellitus. J Clin Invest118, 2148―2156.
|
|
Cooke, R.M., Harvey, T.S., and Campbell, I.D. (1991). Solutionstructure of human insulin-like growth factor 1: a nuclear magneticresonance and restrained molecular dynamics study. Biochemistry30, 5484―5491.
doi: 10.1021/bi00236a022
|
|
Dai, Y., and Tang, J.G. (1996). Characteristic,activity and conformational studies of [A6-Ser, A11-Ser]-insulin. Biochim Biophys Acta1296, 63―68.
|
|
De Meyts, P. (1994). The structural basis of insulin and insulin-like growthfactor-I receptor binding and negative co-operativity, and its relevanceto mitogenic versus metabolic signalling. Diabetologia37, S135―S148.
doi: 10.1007/BF00400837
|
|
De Meyts, P., and Whittaker, J. (2002). Structuralbiology of insulin and IGF1 receptors: implications for drug design. Nat Rev Drug Discov1, 769―783.
doi: 10.1038/nrd917
|
|
De Wolf, E., Gill, R., Geddes, S., Pitts, J., Wollmer, A., and Gr?tzinger, J. (1996). Solutionstructure of a mini IGF-1. Protein Sci5, 2193―2202.
doi: 10.1002/pro.5560051106
|
|
Derewenda, U., Derewenda, Z., Dodson, E.J., Dodson, G.G., Bing, X., and Markussen, J. (1991). X-rayanalysis of the single chain B29-A1 peptide-linked insulin molecule.A completely inactive analogue. J Mol Biol220, 425―433.
doi: 10.1016/0022-2836(91)90022-X
|
|
Derewenda, U., Derewenda, Z., Dodson, E.J., Dodson, G.G., Reynolds, C.D., Smith, G.D., Sparks, C., and Swenson, D. (1989). Phenolstabilizes more helix in a new symmetrical zinc insulin hexamer. Nature338, 594―596.
doi: 10.1038/338594a0
|
|
Dobson, C.M. (1999). Protein misfolding, evolution and disease. Trends Biochem Sci24, 329―332.
doi: 10.1016/S0968-0004(99)01445-0
|
|
Dodson, G., and Steiner, D. (1998). Therole of assembly in insulin's biosynthesis. Curr Opin Struct Biol8, 189―194.
doi: 10.1016/S0959-440X(98)80037-7
|
|
Du, Y.C., Jiang, R.Q., and Tsou, C.L. (1965). Conditions for successfulresynthesis of insulin from its glycyl and phenylalanyl chains. Sci Sin14, 229―236.
|
|
Duret, L., Guex, N., Peitsch, M.C., and Bairoch, A. (1998). New insulin-like proteins with atypical disulfide bondpattern characterized in Caenorhabditis elegans by comparative sequence analysis and homology modeling. Genome Res8, 348―353.
|
|
Edghill, E.L., Flanagan, S.E., Patch, A.M., Boustred, C., Parrish, A., Shields, B., Shepherd, M.H., Hussain, K., Kapoor, R.R., Malecki, M., et al.,and the Neonatal Diabetes International Collaborative Group. (2008). Insulin mutation screening in 1,044 patientswith diabetes: mutations in the INS gene are a common cause of neonataldiabetes but a rare cause of diabetes diagnosed in childhood or adulthood. Diabetes57, 1034―1042.
doi: 10.2337/db07-1405
|
|
Eigenbrot, C., Randal, M., Quan, C., Burnier, J., O”Connell, L., Rinderknecht, E., and Kossiakoff, A.A. (1991). X-raystructure of human relaxin at 1.5?A. Comparison to insulinand implications for receptor binding determinants. J Mol Biol221, 15―21.
|
|
Feng, Y., Liu, D., and Wang, J. (2003). Native-like partiallyfolded conformations and folding process revealed in the N-terminallarge fragments of staphylococcal nuclease: a study by NMR spectroscopy. J Mol Biol330, 821―837.
doi: 10.1016/S0022-2836(03)00660-0
|
|
Feng, Y.M. (2010). Chinese work on insulin (Kerala, India: Transworld ResearchNetwork).
|
|
Gill, R., Verma, C., Wallach, B., Urs?, B., Pitts, J., Wollmer, A., De Meyts, P., and Wood, S. (1999). Modellingof the disulphide-swapped isomer of human insulin-like growth factor-1:implications for receptor binding. ProteinEng12, 297―303.
doi: 10.1093/protein/12.4.297
|
|
Guo, Z.Y., and Feng, Y.M. (2001). Effectsof cysteine to serine substitutions in the two inter-chain disulfidebonds of insulin. Biol Chem382, 443―448.
doi: 10.1515/BC.2001.054
|
|
Guo, Z.Y., Qiao, Z.S., and Feng, Y.M. (2008). The in vitro oxidative folding of the insulinsuperfamily. Antioxid Redox Signal10, 127―139.
doi: 10.1089/ars.2007.1860
|
|
Hober, S., Uhlén, M., and Nilsson, B. (1997). Disulfide exchangefolding of disulfide mutants of insulin-like growth factor I in vitro. Biochemistry36, 4616―4622.
doi: 10.1021/bi9611265
|
|
Hua, Q.X. (2004). Insight into folding, binding and stability of insulinby NMR. Prog Biochem Biophys31, 1―26.
|
|
Hua, Q.X., Chu, Y.C., Jia, W., Phillips, N.F., Wang, R.Y., Katsoyannis, P.G., and Weiss, M.A. (2002a). Mechanism of insulin chain combination. Asymmetric rolesof A-chain alpha-helices in disulfide pairing. J Biol Chem277, 43443―43453.
doi: 10.1074/jbc.M206107200
|
|
Hua, Q.X., Gozani, S.N., Chance, R.E., Hoffmann, J.A., Frank, B.H., and Weiss, M.A. (1995). Structure of a proteinin a kinetic trap. Nat Struct Biol2, 129―138.
doi: 10.1038/nsb0295-129
|
|
Hua, Q.X., Hu, S.Q., Frank, B.H., Jia, W., Chu, Y.C., Wang, S.H., Burke, G.T., Katsoyannis, P.G., and Weiss, M.A. (1996a). Mapping the functional surface of insulin by design:structure and function of a novel A-chain analogue. J Mol Biol264, 390―403.
doi: 10.1006/jmbi.1996.0648
|
|
Hua, Q.X., Jia, W., Frank, B.H., Phillips, N.F., and Weiss, M.A. (2002b). A proteincaught in a kinetic trap: structures and stabilities of insulin disulfideisomers. Biochemistry41, 14700―14715.
doi: 10.1021/bi0202981
|
|
Hua, Q.X., Kochoyan, M., and Weiss, M.A. (1992a). Structure and dynamicsof des-pentapeptide-insulin insolution: the molten-globule hypothesis. Proc Natl Acad Sci U S A89, 2379―2383.
doi: 10.1073/pnas.89.6.2379
|
|
Hua, Q.X., Liu, M., Hu, S.Q., Jia, W., Arvan, P., and Weiss, M.A. (2006a). A conserved histidine in insulin is required for thefoldability of human proinsulin: structure and function of an ALAB5 analog. J Biol Chem281, 24889―24899.
doi: 10.1074/jbc.M602617200
|
|
Hua, Q.X., Mayer, J.P., Jia, W., Zhang, J., and Weiss, M.A. (2006b). Thefolding nucleus of the insulin superfamily: a flexible peptide modelforeshadows the native state. J Biol Chem281, 28131―28142.
doi: 10.1074/jbc.M602616200
|
|
Hua, Q.X., Nakagawa, S.H., Hu, S.Q., Jia, W., Wang, S., and Weiss, M.A. (2006c). Toward the active conformation of insulin: stereospecificmodulation of a structural switch in the B-chain. J Biol Chem281, 24900―24909.
doi: 10.1074/jbc.M602691200
|
|
Hua, Q.X., Nakagawa, S.H., Jia, W., Hu, S.Q., Chu, Y.C., Katsoyannis, P.G., and Weiss, M.A. (2001). Hierarchicalprotein folding: asymmetric unfolding of an insulin analogue lackingthe A7-B7 interchain disulfide bridge. Biochemistry40, 12299―12311.
doi: 10.1021/bi011021o
|
|
Hua, Q.X., Nakagawa, S.H., Jia, W., Huang, K., Phillips, N.B., Hu, S.Q., and Weiss, M.A. (2008). Design of an active ultrastable single-chain insulinanalog: synthesis, structure, and therapeutic implications. J Biol Chem283, 14703―14716.
doi: 10.1074/jbc.M800313200
|
|
Hua, Q.X., Nakagawa, S.H., Wilken, J., Ramos, R.R., Jia, W., Bass, J., and Weiss, M.A. (2003). A divergent INS protein in Caenorhabditiselegans structurally resembles human insulin and activatesthe human insulin receptor. Genes Dev17, 826―831.
doi: 10.1101/gad.1058003
|
|
Hua, Q.X., Narhi, L., Jia, W., Arakawa, T., Rosenfeld, R., Hawkins, N., Miller, J.A., and Weiss, M.A. (1996b). Nativeand non-native structure in a protein-folding intermediate: spectroscopicstudies of partially reduced IGF-I and an engineered alanine model. J Mol Biol259, 297―313.
doi: 10.1006/jmbi.1996.0320
|
|
Hua, Q.X., Shoelson, S.E., Kochoyan, M., and Weiss, M.A. (1991). Receptor binding redefined by a structural switch ina mutant human insulin. Nature354, 238―241.
doi: 10.1038/354238a0
|
|
Hua, Q.X., Shoelson, S.E., and Weiss, M.A. (1992b). Nonlocal structuralperturbations in a mutant human insulin: sequential resonance assignmentand 13C-isotope-aided 2D-NMR studies of [PheB24—>Gly]insulinwith implications for receptor recognition. Biochemistry31, 11940―11951.
doi: 10.1021/bi00162a037
|
|
Hua, Q.X., and Weiss, M.A. (1991). Comparative2D NMR studies of human insulin and des-pentapeptide insulin: sequential resonance assignment and implicationsfor protein dynamics and receptor recognition. Biochemistry30, 5505―5515.
doi: 10.1021/bi00236a025
|
|
Hua, Q.X., and Weiss, M.A. (2004). Mechanismof insulin fibrillation: the structure of insulin under amyloidogenicconditions resembles a protein-folding intermediate. J Biol Chem279, 21449―21460.
doi: 10.1074/jbc.M314141200
|
|
Hua, Q.X., Xu, B., Huang, K., Hu, S.Q., Nakagawa, S., Jia, W., Wang, S., Whittaker, J., Katsoyannis, P.G., and Weiss, M.A. (2009). Enhancing the activity of a protein by stereospecificunfolding: conformational life cycle of insulin and its evolutionaryorigins. J Biol Chem284, 14586―14596.
doi: 10.1074/jbc.M900085200
|
|
Huang, K., Chan, S.J., Hua, Q.X., Chu, Y.C., Wang, R., Klaproth, B., Jia, W., Whittaker, J., De Meyts, P., Nakagawa, S.H., et al. (2007). The A-chain of insulin contacts the insert domain of the receptor.Photo-cross-linking and nonstandard mutagenesis of the diabetes-relatedA3 crevice. J Biol Chem282, 35337―35349.
doi: 10.1074/jbc.M705996200
|
|
Huang, K., Dong, J., Phillips, N.B., Carey, P.R., and Weiss, M.A. (2005). Proinsulinis refractory to protein fibrillation: topological protection of aprecursor protein from cross-beta assembly. J Biol Chem280, 42345―42355.
doi: 10.1074/jbc.M507110200
|
|
Huang, K., Maiti, N.C., Phillips, N.B., Carey, P.R., and Weiss, M.A. (2006). Structure-specificeffects of protein topology on cross-beta assembly: studies of insulinfibrillation. Biochemistry45, 10278―10293.
doi: 10.1021/bi060879g
|
|
Huang, K., Xu, B., Hu, S.Q., Chu, Y.C., Hua, Q.X., Qu, Y., Li, B., Wang, S., Wang, R.Y., Nakagawa, S.H., et al. (2004). How insulin binds: the B-chain alpha-helix contacts the L1 beta-helixof the insulin receptor. J Mol Biol341, 529―550.
doi: 10.1016/j.jmb.2004.05.023
|
|
Humbel, R.E. (1990). Insulin-like growth factors I and II. Eur J Biol277, 103―118.
|
|
Izumi, T., Yokota-Hashimoto, H., Zhao, S., Wang, J., Halban, P.A., and Takeuchi, T. (2003). Dominant negativepathogenesis by mutant proinsulin in the Akita diabetic mouse. Diabetes52, 409―416.
doi: 10.2337/diabetes.52.2.409
|
|
Jia, X.Y., Guo, Z.Y., Wang, Y., Xu, Y., Duan, S.S., and Feng, Y.M. (2003). Peptide models of four possible insulin folding intermediateswith two disulfides. Protein Sci12, 2412―2419.
doi: 10.1110/ps.0389303
|
|
Katsoyannis, P.G., and Tometsko, A. (1966). Insulinsynthesis by recombination of A and B-chains: a highly efficient method. Proc Natl Acad Sci U S A55, 1554―1561.
doi: 10.1073/pnas.55.6.1554
|
|
Kobayashi, M., Ohgaku, S., Iwasaki, M., Maegawa, H., Shigeta, Y., and Inouye, K. (1982). Supernormal insulin:[D-PheB24]-insulin with increased affinity for insulin receptors. Biochem Biophys Res Commun107, 329―336.
doi: 10.1016/0006-291X(82)91708-9
|
|
Kristensen, C., Kjeldsen, T., Wiberg, F.C., Sch?ffer, L., Hach, M., Havelund, S., Bass, J., Steiner, D.F., and Andersen, A.S. (1997). Alaninescanning mutagenesis of insulin. J BiolChem272, 12978―12983.
doi: 10.1074/jbc.272.20.12978
|
|
Kurapkat, G., De Wolf, E., Gr?tzinger, J., and Wollmer, A. (1997). Inactive conformation of an insulin despite its wild-typesequence. Protein Sci6, 580―587.
|
|
Kurose, T., Pashmforoush, M., Yoshimasa, Y., Carroll, R., Schwartz, G.P., Burke, G.T., Katsoyannis, P.G., and Steiner, D.F. (1994). Cross-linkingof a B25 azidophenylalanine insulin derivative to the carboxyl-terminalregion of the alpha-subunit of the insulin receptor. Identificationof a new insulin-binding domain in the insulin receptor. J Biol Chem269, 29190―29197.
|
|
Lawrence, M.C., McKern, N.M., and Ward, C.W. (2007). Insulin receptorstructure and its implications for the IGF-1 receptor. Curr Opin Struct Biol17, 699―705.
doi: 10.1016/j.sbi.2007.07.007
|
|
Laws, D.D., Bitter, H.M., Liu, K., Ball, H.L., Kaneko, K., Wille, H., Cohen, F.E., Prusiner, S.B., Pines, A., and Wemmer, D.E. (2001). Solid-stateNMR studies of the secondary structure of a mutant prion protein fragmentof 55 residues that induces neurodegeneration. Proc Natl Acad Sci USA98, 11686―11690.
doi: 10.1073/pnas.201404298
|
|
Liang, D.C., Chang, W.R., Zhang, J.P., and Wan, Z.L. (1992). The possible mechanism of binding interaction of insulinmolecule with its receptor. Sci China B35, 547―557.
|
|
Lou, M., Garrett, T.P., McKern, N.M., Hoyne, P.A., Epa, V.C., Bentley, J.D., Lovrecz, G.O., Cosgrove, L.J., Frenkel, M.J., and Ward, C.W. (2006). The first three domains of the insulin receptor differstructurally from the insulin-like growth factor 1 receptor in theregions governing ligand specificity. ProcNatl Acad Sci U S A103, 12429―12434.
doi: 10.1073/pnas.0605395103
|
|
McKern, N.M., Lawrence, M.C., Streltsov, V.A., Lou, M.Z., Adams, T.E., Lovrecz, G.O., Elleman, T.C., Richards, K.M., Bentley, J.D., Pilling, P.A., et al. (2006). Structure of the insulin receptor ectodomain reveals a folded-overconformation. Nature443, 218―221.
doi: 10.1038/nature05106
|
|
Miller, J.A., Narhi, L.O., Hua, Q.X., Rosenfeld, R., Arakawa, T., Rohde, M., Prestrelski, S., Lauren, S., Stoney, K.S., Tsai, L., et al. (1993). Oxidative refolding of insulin-like growth factor 1yields two products of similar thermodynamic stability: a bifurcatingprotein-folding pathway. Biochemistry32, 5203―5213.
doi: 10.1021/bi00070a032
|
|
Milner, S.J., Carver, J.A., Ballard, F.J., and Francis, G.L. (1999). Probing the disulfide folding pathway of insulin-likegrowth factor-I. Biotechnol Bioeng62, 693―703.
doi: 10.1002/(SICI)1097-0290(19990320)62:6<693::AID-BIT8>3.0.CO;2-S
|
|
Molven, A., Ringdal, M., Nordb?, A.M., Raeder, H., St?y, J., Lipkind, G.M., Steiner, D.F., Philipson, L.H., Bergmann, I., Aarskog, D., et al.,and the Norwegian Childhood Diabetes Study Group. (2008). Mutations in the insulin gene can cause MODY and autoantibody-negativetype 1 diabetes. Diabetes57, 1131―1135.
doi: 10.2337/db07-1467
|
|
Murray-Rust, J., McLeod, A.N., Blundell, T.L., and Wood, S.P. (1992). Structure and evolution of insulins: implications forreceptor binding. Bioessays14, 325―331.
doi: 10.1002/bies.950140507
|
|
Nagata, K., Hatanaka, H., Kohda, D., Kataoka, H., Nagasawa, H., Isogai, A., Ishizaki, H., Suzuki, A., and Inagaki, F. (1995a). Identificationof the receptor-recognition surface of bombyxin-II, an insulin-likepeptide of the silkmoth Bombyx mori: critical importance of the B-chaincentral part. J Mol Biol253, 759―770.
doi: 10.1006/jmbi.1995.0589
|
|
Nagata, K., Hatanaka, H., Kohda, D., Kataoka, H., Nagasawa, H., Isogai, A., Ishizaki, H., Suzuki, A., and Inagaki, F. (1995b). Three-dimensionalsolution structure of bombyxin-II an insulin-like peptide of the silkmothBombyx mori: structural comparison with insulin and relaxin. J Mol Biol253, 749―758.
doi: 10.1006/jmbi.1995.0588
|
|
Nakagawa, S.H., and Tager, H.S. (1991). Implicationsof invariant residue LeuB6 in insulin-receptor interactions. J Biol Chem266, 11502―11509.
|
|
Nakagawa, S.H., and Tager, H.S. (1992). Importanceof aliphatic side-chain structure at positions 2 and 3 of the insulinA chain in insulin-receptor interactions. Biochemistry31, 3204―3214.
doi: 10.1021/bi00127a023
|
|
Nakagawa, S.H., Zhao, M., Hua, Q.X., Hu, S.Q., Wan, Z.L., Jia, W., and Weiss, M.A. (2005). Chiralmutagenesis of insulin. Foldability and function are inversely regulatedby a stereospecific switch in the B-chain. Biochemistry44, 4984―4999.
doi: 10.1021/bi048025o
|
|
Nanjo, K., Sanke, T., Miyano, M., Okai, K., Sowa, R., Kondo, M., Nishimura, S., Iwo, K., Miyamura, K., Given, B.D., et al. (1986). Diabetes due to secretion of a structurally abnormal insulin (insulinWakayama). Clinical and functional characteristics of [LeuA3] insulin. J Clin Invest77, 514―519.
doi: 10.1172/JCI112331
|
|
Narhi, L.O., Hua, Q.X., Arakawa, T., Fox, G.M., Tsai, L., Rosenfeld, R., Holst, P., Miller, J.A., and Weiss, M.A. (1993). Role of native disulfide bonds in the structure andactivity of insulin-like growth factor 1: genetic models of protein-foldingintermediates. Biochemistry32, 5214―5221.
doi: 10.1021/bi00070a033
|
|
Nielsen, L., Khurana, R., Coats, A., Frokjaer, S., Brange, J., Vyas, S., Uversky, V.N., and Fink, A.L. (2001). Effectof environmental factors on the kinetics of insulin fibril formation:elucidation of the molecular mechanism. Biochemistry40, 6036―6046.
doi: 10.1021/bi002555c
|
|
Oyadomari, S., Koizumi, A., Takeda, K., Gotoh, T., Akira, S., Araki, E., and Mori, M. (2002). Targeted disruption of the Chop gene delays endoplasmicreticulum stress-mediated diabetes. J ClinInvest109, 525―532.
|
|
Peking, I.R.G. (1971). Insulin's crystal structure at 2.5Aresolution. Peking Rev40, 11―16.
|
|
Pierce, S.B., Costa, M., Wisotzkey, R., Devadhar, S., Homburger, S.A., Buchman, A.R., Ferguson, K.C., Heller, J., Platt, D.M., Pasquinelli, A.A., et al.(2001). Regulation of DAF-2 receptor signalingby human insulin and ins-1, a member of the unusually large and diverse C. elegans insulin gene family. Genes Dev15, 672―686.
doi: 10.1101/gad.867301
|
|
Pullen, R.A., Lindsay, D.G., Wood, S.P., Tickle, I.J., Blundell, T.L., Wollmer, A., Krail, G., Brandenburg, D., Zahn, H., Gliemann, J., et al. (1976). Receptor-binding region of insulin. Nature259, 369―373.
doi: 10.1038/259369a0
|
|
Qiao, Z.S., Guo, Z.Y., and Feng, Y.M. (2001). Putative disulfide-formingpathway of porcine insulin precursor during its refolding in vitro. Biochemistry40, 2662―2668.
doi: 10.1021/bi001613r
|
|
Qiao, Z.S., Guo, Z.Y., and Feng, Y.M. (2006). In vitro folding/unfolding of insulin/single-chain insulin. Protein Pept Lett13, 423―429.
doi: 10.2174/092986606776819583
|
|
Qiao, Z.S., Min, C.Y., Hua, Q.X., Weiss, M.A., and Feng, Y.M. (2003). In vitro refolding of human proinsulin. Kineticintermediates, putative disulfide-forming pathway folding initiationsite, and potential role of C-peptide in folding process. J Biol Chem278, 17800―17809.
doi: 10.1074/jbc.M300906200
|
|
Ron, D. (2002). Proteotoxicity in the endoplasmic reticulum: lessonsfrom the Akita diabetic mouse. J Clin Invest109, 443―445.
|
|
Sato, A., Koyama, S., Yamada, H., Suzuki, S., Tamura, K., Kobayashi, M., Niwa, M., Yasuda, T., Kyogoku, Y., and Kobayashi, Y. (2000). Three-dimensionalsolution structure of a disulfide bond isomer of the human insulin-likegrowth factor-I. J Pept Res56, 218―230.
doi: 10.1034/j.1399-3011.2000.00769.x
|
|
Sato, A., Nishimura, S., Ohkubo, T., Kyogoku, Y., Koyama, S., Kobayashi, M., Yasuda, T., and Kobayashi, Y. (1993). Three-dimensionalstructure of human insulin-like growth factor-I (IGF-I) determinedby 1H-NMR and distance geometry. Int JPept Protein Res41, 433―440.
|
|
Sch?ffer, L. (1994). A model for insulin binding to the insulin receptor. Eur J Biochem221, 1127―1132.
doi: 10.1111/j.1432-1033.1994.tb18833.x
|
|
Shoelson, S.E., Lu, Z.X., Parlautan, L., Lynch, C.S., and Weiss, M.A. (1992). Mutationsat the dimer, hexamer, and receptor-binding surfaces of insulin independentlyaffect insulin-insulin and insulin-receptor interactions. Biochemistry31, 1757―1767.
doi: 10.1021/bi00121a025
|
|
Sieber, P.S., Eisler, K., Kamber, B., Riniker, B., Rittel, W., M?rki, F., and de Gasparo, M. (1978). Synthesis and biological activity of two disulphidebond isomers of human insulin: [A7―A11,A6―B7-cystine]-and [A6―A7,A11―B7-cystine]insulin (human). Hoppe Seylers Z Physiol Chem359, 113―123.
|
|
Steiner, D.F. (1967). Evidence for a precursor in the biosynthesis of insulin. Trans N Y Acad Sci30, 60―68.
|
|
Steiner, D.F. (1998). The proprotein convertases. Curr Opin Chem Biol2, 31―39.
doi: 10.1016/S1367-5931(98)80033-1
|
|
Steiner, D.F., Tager, H.S., Chan, S.J., Nanjo, K., Sanke, T., and Rubenstein, A.H. (1990). Lessonslearned from molecular biology of insulin-gene mutations. Diabetes Care13, 600―609.
doi: 10.2337/diacare.13.6.600
|
|
St?y, J., Edghill, E.L., Flanagan, S.E., Ye, H., Paz, V.P., Pluzhnikov, A., Below, J.E., Hayes, M.G., Cox, N.J., Lipkind, G.M., et al., and the Neonatal DiabetesInternational Collaborative Group. (2007). Insulin gene mutations as a cause of permanent neonatal diabetes. Proc Natl Acad Sci U S A104, 15040―15044.
doi: 10.1073/pnas.0707291104
|
|
Tang, J.G., and Tsou, C.L. (1990). Theinsulin A and B-chains contain structural information for the formationof the native molecule. Studies with protein disulphide-isomerase. Biochem J268, 429―435.
|
|
Torres, A.M., Forbes, B.E., Aplin, S.E., Wallace, J.C., Francis, G.L., and Norton, R.S. (1995). Solution structureof human insulin-like growth factor II. Relationship to receptor andbinding protein interactions. J Mol Biol248, 385―401.
doi: 10.1016/S0022-2836(95)80058-1
|
|
Vajo, Z., and Duckworth, W.C. (2000). Geneticallyengineered insulin analogs: diabetes in the new millenium. Pharmacol Rev52, 1―9.
|
|
Wan, Z.L., Huang, K., Hu, S.Q., Whittaker, J., and Weiss, M.A. (2008). Thestructure of a mutant insulin uncouples receptor binding from proteinallostery. An electrostatic block to the TR transition. J Biol Chem283, 21198―21210.
doi: 10.1074/jbc.M800235200
|
|
Wang, C.C., and Tsou, C.L. (1991). Theinsulin A and B-chains contain sufficient structural information toform the native molecule. Trends BiochemSci16, 279―281.
doi: 10.1016/0968-0004(91)90114-B
|
|
Wang, D.C.G., and Gu, X.C. (2010). A briefaccount on the study of the insulin crystal structure. Sin China Series C53, 13―15.
doi: 10.1007/s11427-010-0019-2
|
|
Wang, J., Takeuchi, T., Tanaka, S., Kubo, S.K., Kayo, T., Lu, D., Takata, K., Koizumi, A., and Izumi, T. (1999). A mutation in the insulin 2 gene induces diabetes withsevere pancreatic beta-cell dysfunction in the Mody mouse. J Clin Invest103, 27―37.
doi: 10.1172/JCI4431
|
|
Ward, C., Lawrence, M.C., Streltsov, V., Garrett, T., McKern, N., Lou, M.Z., Lovrecz, G., and Adams, T. (2008). Structuralinsights into ligand-induced activation of the insulin receptor. Acta Physiol (Oxf)192, 3―9.
|
|
Waugh, D.F. (1941). The properties of protein fibers produced. Reversiblyfrom soluble protein molecules. Am J Physiol133, 484―P485.
|
|
Waugh, D.F. (1944). The linkage of corpuscular protein molecules. I. A fibrousmodification on insulin. J Am Chem Soc66, 663.
doi: 10.1021/ja01232a516
|
|
Waugh, D.F. (1946a). Fed Proc5, 111.
|
|
Waugh, D.F. (1946b). A fibrous modification of insulin. I. The heat precipitateof insulin. J Am Chem Soc68, 247―250.
doi: 10.1021/ja01206a030
|
|
Weiss, M.A., Hua, Q.X., Jia, W., Chu, Y.C., Wang, R.Y., and Katsoyannis, P.G. (2000). Hierarchical protein "un-design": insulin's intrachain disulfide bridge tethers a recognition alpha-helix. Biochemistry39, 15429―15440.
doi: 10.1021/bi001905s
|
|
Weiss, M.A., Hua, Q.X., Lynch, C.S., Frank, B.H., and Shoelson, S.E. (1991). Heteronuclear2D NMR studies of an engineered insulin monomer: assignment and characterizationof the receptor-binding surface by selective 2H and 13C labeling with application toprotein design. Biochemistry30, 7373―7389.
doi: 10.1021/bi00244a004
|
|
Wuthrich, K. (1986). NMR of Proteins and Nucleic Acids (New York, NY: John Wiley &Sons).
|
|
Xu, B., Hu, S.Q., Chu, Y.C., Huang, K., Nakagawa, S.H., Whittaker, J., Katsoyannis, P.G., and Weiss, M.A. (2004a). Diabetes-associatedmutations in insulin: consecutive residues in the B-chain contactdistinct domains of the insulin receptor. Biochemistry43, 8356―8372.
doi: 10.1021/bi0497796
|
|
Xu, B., Hu, S.Q., Chu, Y.C., Wang, S., Wang, R.Y., Nakagawa, S.H., Katsoyannis, P.G., and Weiss, M.A. (2004b). Diabetes-associatedmutations in insulin identify invariant receptor contacts. Diabetes53, 1599―1602.
doi: 10.2337/diabetes.53.6.1599
|
|
Xu, B., Huang, K., Chu, Y.C., Hu, S.Q., Nakagawa, S., Wang, S., Wang, R.Y., Whittaker, J., Katsoyannis, P.G., and Weiss, M.A. (2009). Decoding the cryptic active conformation of a proteinby synthetic photoscanning: insulin inserts a detachable arm betweenreceptor domains. J Biol Chem284, 14597―14608.
doi: 10.1074/jbc.M900087200
|
|
Yan, H., Guo, Z.Y., Gong, X.W., Xi, D., and Feng, Y.M. (2003). A peptide modelof insulin folding intermediate with one disulfide. Protein Sci12, 768―775.
doi: 10.1110/ps.0237203
|
|
Yoshioka, M., Kayo, T., Ikeda, T., and Koizumi, A. (1997). A novel locus, Mody4, distal to D7Mit189 on chromosome7 determines early-onset NIDDM in nonobese C57BL/6 (Akita) mutantmice. Diabetes46, 887―894.
doi: 10.2337/diabetes.46.5.887
|
|
Zahn, H., and Schmidt, G. (1967). Synthesisof an insulin B-chain disulfide polymer. Tetrahedron Lett50, 5095―5098.
doi: 10.1016/S0040-4039(01)89923-8
|
|
Zeng, Z.H., Liu, Y.S., Jin, L., Zhang, Y., Havelund, S., Markussen, J., and Wang, D.C. (2000). Conformational correlation and coupled motion betweenresidue A21 and B25 side chain observed in crystal structures of insulinmutants at position A21. Biochim BiophysActa1479, 225―236.
|
|
Zhang, Y.S. (2010). The first protein ever synthesized in vitro. Sin China Series C53, 16―18.
doi: 10.1007/s11427-010-0008-5
|
|
Viewed |
|
|
|
Full text
|
|
|
|
|
Abstract
|
|
|
|
|
Cited |
|
|
|
|
| |
Shared |
|
|
|
|
| |
Discussed |
|
|
|
|
