How myosin VI traps its off-state, is activated and dimerizes.
How myosin VI traps its off-state, is activated and dimerizes.
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DOI:
10.1038/s41467-023-42376-2
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发表时间:
2023-10-23
影响因子:
16.6
通讯作者:
Houdusse, Anne
中科院分区:
文献类型:
--
作者:
Canon, Louise;Kikuti, Carlos;Planelles-Herrero, Vicente J.;Lin, Tianming;Mayeux, Franck;Sirkia, Helena;Lee, Young il;Heidsieck, Leila;Velikovsky, Leonid;David, Amandine;Liu, Xiaoyan;Moussaoui, Dihia;Forest, Emma;Hook, Peter;Petersen, Karl J.;Morgan, Tomos E.;Di Cicco, Aurelie;Sires-Campos, Julia;Derivery, Emmanuel;Levy, Daniel;Delevoye, Cedric;Sweeney, H. Lee;Houdusse, Anne
Myosin VI (Myo6) is the only minus-end directed nanomotor on actin, allowing it to uniquely contribute to numerous cellular functions. As for other nanomotors, the proper functioning of Myo6 relies on precise spatiotemporal control of motor activity via a poorly defined off-state and interactions with partners. Our structural, functional, and cellular studies reveal key features of myosin regulation and indicate that not all partners can activate Myo6. TOM1 and Dab2 cannot bind the off-state, while GIPC1 binds Myo6, releases its auto-inhibition and triggers proximal dimerization. Myo6 partners thus differentially recruit Myo6. We solved a crystal structure of the proximal dimerization domain, and show that its disruption compromises endocytosis in HeLa cells, emphasizing the importance of Myo6 dimerization. Finally, we show that the L926Q deafness mutation disrupts Myo6 auto-inhibition and indirectly impairs proximal dimerization. Our study thus demonstrates the importance of partners in the control of Myo6 auto-inhibition, localization, and activation. Canon et al. offer insights into the auto-inhibition and activation of the minus-end directed motor myosin VI. The work highlights how differential relief of auto-inhibition allows for fine control of myosin VI activity in vivo.
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影响因子:
4.6
作者:
Bonnet J;Cartannaz J;Tourcier G;Contreras-Martel C;Kleman JP;Morlot C;Vernet T;Di Guilmi AM
通讯作者:
Di Guilmi AM
DOI:
10.1107/s0907444904019158
发表时间:
2004-12-01
影响因子:
2.2
作者:
Emsley, P;Cowtan, K
通讯作者:
Cowtan, K
影响因子:
4.8
作者:
De la Cruz, EM;Ostap, EM;Sweeney, HL
通讯作者:
Sweeney, HL
影响因子:
15
作者:
Barnes, C. Ashley;Shen, Yang;Bax, Ad
通讯作者:
Bax, Ad
DOI:
10.1073/pnas.1315923111
发表时间:
2014-03-18
影响因子:
11.1
作者:
Hariadi, Rizal F.;Cale, Mario;Sivaramakrishnan, Sivaraj
通讯作者:
Sivaramakrishnan, Sivaraj