Unique features of myosin VI: a structural view

doi:10.1007/s11515-010-0048-z

Front Biol

2010, Vol. 5

Issue (3) : 204-210 https://doi.org/10.1007/s11515-010-0048-z

REVIEW

Unique features of myosin VI: a structural view

Wei FENG(

)

National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China

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Abstract

Myosin VI is the only known molecular motor for the transportation of cargo vesicles from the plus end to the minus end of actin filaments. Thus, myosin VI possesses several unique features to distinguish it from other myosin family motors, such as the ability to move in a reverse direction, the unusual large walking step size, and the cargo-mediated dimerization. Recent structural studies of myosin VI have provided mechanistic insights into these unique features. On the basis of the resolved structures of myosin VI each domains (i.e., the structures of the N-terminal motor domain, the C-terminal cargo binding domain, and the region in the middle), the unique features of myosin VI will be reviewed here from a structural perspective. The structural studies of myosin VI definitely provide some answers about the unique features of myosin VI, but also raise significant questions on how myosin VI functions as a special motor both for directional cargo transport and for structural anchoring.

Keywords molecular motor myosin VI cargo transport cargo binding walking step size

Corresponding Author(s): FENG Wei,Email:wfeng@ibp.ac.cn

Issue Date: 01 June 2010

Cite this article:

Wei FENG. Unique features of myosin VI: a structural view[J]. Front Biol, 2010, 5(3): 204-210.

URL:

https://academic.hep.com.cn/fib/EN/10.1007/s11515-010-0048-z
https://academic.hep.com.cn/fib/EN/Y2010/V5/I3/204

Fig.1 . : Domain organization of myosin VI. Myosin VI contains an N-terminal motor domain, a short neck region/lever arm (including a unique insertion and one “IQ” motif), a lever arm extension (LAE) and a single a-helix (SAH) (a putative coiled-coil domain) in the middle, and a C-terminal cargo-binding domain (CBD). : Myosin VI is an actin-filament minus-end-orientated myosin motor and plays diverse roles in a variety of cellular processes, including clathrin-coated/uncoated vesicle-mediated endocytosis and stabilization of the basal region of stereo-cilia, the trans-Golgi complexes, and the nuclear transcription machinery. Myosin VI is shown in a dimeric state with two motor heads attaching to actin-filaments.

Fig.2 . : A ribbon diagram combined with surface representation of the myosin VI motor domain in the ADP/Pi-bound state (the pre-powerstroke state) (PDB code: 2V26). The lever arm not included in the structure is represented by a dash cylinder. : A ribbon diagram combined with surface representation of the motor domain together with the lever arm (including the unique insertion and the “IQ” motif both in complex with the CaM) in the nucleotide-free state (the post-powerstroke state) (PDB code: 2BKI). The motor domain (including the converter/insertion region and the lever arm), the Ca-CaM, and the apo-CaM are colored in purple, orange, and green respectively. From the pre-powerstroke state to the post-powerstroke state, the “converter/insertion” region of the motor undergoes significant conformational changes and the lever arm rotates about 180° re-pointing from the plus end to the minus end of actin-filaments.

Fig.3 . A schematic model showing the dimeric myosin VI walks along actin-filaments with a ~36 nm step size. The synergistic binding between the CBD and the Dab2 (i.e., two continuous helices of Dab2 C-terminal tail tether the two CBD together) results in the dimerization of myosin VI. Interestingly, both the isolated CBD and the isolated Dab2 are monomers, and therefore, myosin VI forms specific dimmers only upon cargo-binding. The large ~36 nm step size of myosin VI might be contributed by both the SAH and the LAE expansion (indicated by the dash arrows). The myosin VI CBD/Dab2 complex structure (PDB code: 3H8D) is in the combined surface and ribbon representations; other domains of myosin VI, the cargo adaptor Dab2, and the cargoes, are all in the cartoon representations for simplicity.

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