Structure of Myosin VI/Tom1 complex reveals a cargo recognition mode of Myosin VI for tethering

Nature Communications
Shichen HuLifeng Pan

Abstract

Myosin VI plays crucial roles in diverse cellular processes. In autophagy, Myosin VI can facilitate the maturation of autophagosomes through interactions with Tom1 and the autophagy receptors, Optineurin, NDP52 and TAX1BP1. Here, we report the high-resolution crystal structure of the C-terminal cargo-binding domain (CBD) of Myosin VI in complex with Tom1, which elucidates the mechanistic basis underpinning the specific interaction between Myosin VI and Tom1, and uncovers that the C-terminal CBD of Myosin VI adopts a unique cargo recognition mode to interact with Tom1 for tethering. Furthermore, we show that Myosin VI can serve as a bridging adaptor to simultaneously interact with Tom1 and autophagy receptors through two distinct interfaces. In all, our findings provide mechanistic insights into the interactions of Myosin VI with Tom1 and relevant autophagy receptors, and are valuable for further understanding the functions of these proteins in autophagy and the cargo recognition modes of Myosin VI.

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Citations

Aug 23, 2020·International Journal of Molecular Sciences·Marianne IbrahimFabrice Bertile
Jan 3, 2021·Histochemistry and Cell Biology·Przemysław ZakrzewskiFolma Buss
Oct 15, 2020·Current Opinion in Structural Biology·Elisa Magistrati, Simona Polo
Mar 16, 2021·Frontiers in Cell and Developmental Biology·Tiffany G RoachDaniel G S Capelluto
Feb 23, 2020·Mechanisms of Ageing and Development·Konstantinos Palikaras, Nektarios Tavernarakis

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Methods Mentioned

BETA
light-scattering
gel filtration
nuclear magnetic resonance
isothermal titration calorimetry
gel
NMR
co-immunoprecipitation
Co-IP
gel-filtration
electrophoresis

Software Mentioned

PHENIX
PHASER
SEDFIT
HKL2000
Micro Cal
ASTRA
MolProbity
REFMAC
PyMOL
Origin

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