Structural biology study of human TNF receptor associated factor 4 TRAF domain

doi:10.1007/s13238-013-3068-z

Prot Cell

2013, Vol. 4

Issue (9) : 687-694 https://doi.org/10.1007/s13238-013-3068-z

RESEARCH ARTICLE

Structural biology study of human TNF receptor associated factor 4 TRAF domain

Fengfeng Niu^1,3, Heng Ru^1,2, Wei Ding¹, Songying Ouyang¹(

), Zhi-Jie Liu^1,2(

)

1. National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China; 2. Institute of Molecular and Clinical Medicine, Kunming Medical University, Kunming 650500, China; 3. University of Chinese Academy of Sciences, Beijing 100049, China

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Abstract

TRAF4 is a unique member of TRAF family, which is essential for innate immune response, nervous system and other systems. In addition to being an adaptor protein, TRAF4 was identifi ed as a regulator protein in recent studies. We have determined the crystal structure of TRAF domain of TRAF4 (residues 292-466) at 2.60 ? resolution by X-ray crystallography method. The trimericly assembled TRAF4 resembles a mushroom shape, containing a super helical “stalk” which is made of three right-handed intertwined α helixes and a C-terminal “cap”, which is divided at residue L302 as a boundary. Similar to other TRAFs, both intermolecular hydrophobic interaction in super helical “stalk” and hydrogen bonds in “cap” regions contribute directly to the formation of TRAF4 trimer. However, differing from other TRAFs, there is an additional flexible loop (residues 421-426), which contains a previously identified phosphorylated site S426 exposing on the surface. This S426 was reported to be phosphorylated by IKKα which is the pre-requisite for TRAF4-NOD2 complex formation and thus to inhibit NOD2-induced NF-κB activation. Therefore, the crystal structure of TRAF4-TRAF is valuable for understanding its molecular basis for its special function and provides structural information for further studies.

Keywords TRAF4 TRAF domain crystal structure additional loop phosphorylation site

Corresponding Author(s): Ouyang Songying,Email:ouyangsy@moon.ibp.ac.cn; Liu Zhi-Jie,Email:zjliu@ibp.ac.cn

Issue Date: 01 September 2013

Cite this article:

Fengfeng Niu,Heng Ru,Wei Ding, et al. Structural biology study of human TNF receptor associated factor 4 TRAF domain[J]. Prot Cell, 2013, 4(9): 687-694.

URL:

https://academic.hep.com.cn/pac/EN/10.1007/s13238-013-3068-z
https://academic.hep.com.cn/pac/EN/Y2013/V4/I9/687

1	Adams, P.D., Afonine, P.V., Bunkoczi, G., Chen, V.B., Davis, I.W., Echols, N., Headd, J.J., Hung, L.-W., Kapral, G.J., and GrosseKunstleve, R.W. (2010). PHE NIX: a comprehensive Python-based system for macromolecular structure solution. Acta Crystallogr D Biol Crystallogr 66, 213-221 . doi: 10.1107/S0907444909052925
2	Bouwmeester, T., Bauch, A., Ruffner, H., Angrand, P.-O., Bergamini, G., Croughton, K., Cruciat, C., Eberhard, D., Gagneur, J., and Ghidelli, S. (2004). A p hysical and functional map of the human TNF-d, P.-O., Bergamini, G., Croughton,. Nat Cell Biol 6, 97-105 . doi: 10.1038/ncb1086
3	Bradley, J.R., and Pober, J.S. (2001). Tumor necrosis factor receptorassociated factors (TRAFs). Oncogene 20, 6482-6491 . doi: 10.1038/sj.onc.1204788
4	Chung, J.Y., Park, Y.C., Ye, H., and Wu, H. (2002). AllTRAFs are not created equal: common and distinct molecular mechanisms of TRAF-mediated signal transduction. J Cell Sci 115, 679-688 .
5	Dephoure, N., Zhou, C., Vill H .,and Wu, H. (2002). All TRAFs are not created equal: common and distinct molecular mechative atlas of mitotic phosphorylation. Proc Natl Acad Sci U S A 105, 10762-10767 . doi: 10.1073/pnas.0805139105
6	Emsley, P., Lohkamp, B., Scott, W., and Cowtan, K. (2010). Features and development of Coot. Acta Crystallogr D Biol Crystallogr 66, 486-501 . doi: 10.1107/S0907444910007493
7	Holm, L., and Rosenstr., Scott, W., and Cowtan, K. (2010). Dali server: conservation mapping in 3D. Nucleic Acids Res 38, W545-W549 . doi: 10.1093/nar/gkq366
8	Inoue, J., Ishida, T., Tsukamoto, N., Kobayashi, N., Naito, A., Azuma, S., and Yamamoto, T. (2000). Tumor necrosis factor receptor-associated factor (TRAF) family: adapter proteins that mediate cytokine signaling. Exp Cell Res 254, 14. doi: 10.1006/excr.1999.4733
9	Kedinger, V., and Rio, M.C. (2007). TRAF4, the unique family member. In TNF Receptor Associated Factors (TRAFs) (Springer) ,pp. 60-71 . doi: 10.1007/978-0-387-70630-6_5
10	Krajewska, M., Krajewski, S., Zapata, J.M., Van Arsdale, T., Gascoyne, R.D., Berern, K., McFadden, D., Shabaik, A., Hugh, J., and Reynolds, A. (1998). TRA F-4 expression in epithelial progenitor cells. Analysis in normal adult, fetal, and tumor tissues. Am J Pathol 152, 1549.
11	Krissinel, E., and Henrick, K. (2007). In ference of macromolecular assemblies from crystalline state. J Mol Biol 372, 774-797 . doi: 10.1016/j.jmb.2007.05.022
12	Li, J.M., Fan, L.M., Christie, M.R., and Shah, A.M. (2005). Acute tumor necrosis factor alpha signaling via NADPH oxidase in microvascular endothelial cells: role of p47phox phosphorylation and binding to TRAF4. Mol Cell Biol 25, 2320-2330 . doi: 10.1128/MCB.25.6.2320-2330.2005
13	Marinis, J.M., Homer, C.R., McDonald, C., and Abbott, D.W. (2011). An ovel motif in the Crohn’s disease susceptibility protein, NOD2, allows TRAF4 to down-regulate innate immune responses. J Biol Chem 286, 1938-1950 . doi: 10.1074/jbc.M110.189308
14	Marinis, J.M., Hutti, J.E., Homer, C.R., Cobb, B.A., Cantley, L.C., McDonald, C., and Abbott, D.W. (2012). IκB Kinase α Phosphorylation of TRAF4 Downregulates Innate Immune Signaling. Mol Cell Biol 32, 2479-2489 . doi: 10.1128/MCB.00106-12
15	McCoy, A.J., Grosse-Kunstleve, R.W., Adams, P.D., Winn, M.D., Storoni, L.C., and Read, R.J. (2007). Pha ser crystallographic software. J Appl Crystallogr 40, 658-674 . doi: 10.1107/S0021889807021206
16	McWhirter, S.M., Pullen, S.S., Holton, J.M., Crute, J.J., Kehry, M.R., and Alber, T. (1999). Cry stallographic analysis of CD40 recognition and signaling by human TRAF2. Proc Natl Acad Sci U S A 96, 8408-8413 . doi: 10.1073/pnas.96.15.8408
17	Murshudov, G.N., Vagin, A.A., and Dodson, E.J. (1997). Refinement of macromolecular structures by the maximum-likelihood method. Acta Crystallogr D Biol Crystallogr 53, 240-255 . doi: 10.1107/S0907444996012255
18	Ni, C.-Z., Welsh, K., Leo, E., Chiou, C.-k., Wu, H., Reed, J.C., and Ely, K.R. (2000). Molecular basis for CD40 signaling mediated by TRAF3. Proc Natl Acad Sci U S A 97, 10395-10399 . doi: 10.1073/pnas.97.19.10395
19	Olsen, J.V., Vermeulen, M., Santamaria, A., Kumar, C., Miller, M.L., Jensen, L.J., Gnad, F., Cox, J., Jensen, T.S., and Nigg, E.A. (2010). Qua ntitative phosphoproteomics reveals widespread full phosphor rylation site occupancy during mitosis. Sci Signal 3, ra3. doi: 10.1126/scisignal.2000475
20	Otwinowski, Z., and Minor, W. (1997). Processing of X-ray diffraction data. Methods enzymol 276, 307-326 . doi: 10.1016/S0076-6879(97)76066-X
21	Park, Y.C., Burkitt, V., Villa, A.R., Tong, L., and Wu, H. (1999). Structural basis for self-association and receptor recognition of human TRAF2. Nature 398, 533-538 . doi: 10.1038/19110
22	Park, Y.C., Ye, H., Hsia, C., Segal, D., Rich, R.L., Liou, H.-C., Myszka, D.G., and Wu, H. (2000). A novel mechanism of TRAF signaling revealed by structural and functional analyses of the TRADD-TRAF2 interaction. Cell 101, 777-787 . doi: 10.1016/S0092-8674(00)80889-2
23	Régnier, C.H., Tomasetto, C., Moog-Lutz, C., Chenard, M.-P., Wendling, C., Basset, P., and Rio, M.-C. (1995). Presence of a new conserved domain in CART1, a novel member of the tumor necrosis factor receptor-associated protein family, which is expressed in breast carcinoma. J Biol Chem 270, 25715-25721 . doi: 10.1074/jbc.270.43.25715
24	Wajant, H., Henkler, F., and Scheurich, P. (2001). The TNF-receptorassociated factor family: scaffold molecules for cytokine receptors, kinases and their regulators. Cell Signal 13, 389-400 . doi: 10.1016/S0898-6568(01)00160-7
25	Wu, H. (2007). TNF receptor associated factors (TRAFs),Vol 597 (Springer). doi: 10.1007/978-0-387-70630-6
26	Xie, P. (2013). TRA F molecules in cell signaling and in human diseases. J Mol Signal 8, 7. doi: 10.1186/1750-2187-8-7
27	Ye, H., Arron, J.R., Lamothe, B., Cirilli, M., Kobayashi, T., Shevde, N.K., Segal, D., Dzivenu, O.K., Vologodskaia, M., and Yim, M. (2002). Distinct molecular mechanism for initiating TRAF6 signalling. Nature 418, 443-447 . doi: 10.1038/nature00888
28	Ye, H., Park, Y.C., Kreishman, M., Kieff, E., and Wu, H. (1999a). The structural basis for the recognition of diverse receptor sequences by TRAF2. Mol Cell 4, 321-330 . doi: 10.1016/S1097-2765(00)80334-2
29	Ye, X., Mehlen, P., Rabizadeh, S., VanArsdale, T., Zhang, H., Shin, H., Wang, J.J., Leo, E., Zapata, J., and Hauser, C.A. (1999b). TRAF family proteins interact with the common neurotrophin receptor and modulate apoptosis induction. J Biol Chem 274, 30202-30208 . doi: 10.1074/jbc.274.42.30202
30	Yin, Q., Lin, S.-C., Lamothe, B., Lu, M., Lo, Y.-C., Hura, G., Zheng, L., Rich, R.L., Campos, A.D., and Myszka, D.G. (2009). E2 interaction and dimerization in the crystal structure of TRAF6. Nat Struct Mol Biol 16, 658-666 . doi: 10.1038/nsmb.1605
31	Zepp, J.A., Liu, C., Qian, W., Wu, L., Gulen, M.F., Kang, Z., and Li, X. (2012). Cut ting edge: TNF receptor-associated factor 4 restricts IL-17-mediated pathology and signaling processes. J Immunol 189, 33-37 . doi: 10.4049/jimmunol.1200470
32	Zhang, P., Reichardt, A., Liang, H., Aliyari, R., Cheng, D., Wang, Y., Xu, F., Cheng, G., and Liu, Y. (2012). Single amino acid substitutions confer the antiviral activity of the TRAF3 adaptor protein onto TRAF5. Sci Signal 5, ra81. doi: 10.1126/scisignal.2003152
33	Zheng, C., Kabaleeswaran, V., Wang, Y., Cheng, G., and Wu, H. (2010). Crystal structures of the TRAF2: cIAP2 and the TRAF1: TRAF2: cIAP2 complexes: affi nity, specifi city, and regulation. Mol Cell 38, 101-113 . doi: 10.1016/j.molcel.2010.03.009
34	Zotti, T., and Vito, P. (2012). The seventh ring: exploring TRAF7 functions. J Cell Physiol 227, 1280-1284 . doi: 10.1002/jcp.24011

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