8ARD

Myosin VI proximal tail domain, dimeric

8ARD の概要

• エントリーDOI: 10.2210/pdb8ard/pdb
• 分子名称: Unconventional myosin-VI (2 entities in total)
• 機能のキーワード: dimer, myosin vi, myo6, motor protein
• 由来する生物種: Mus musculus (house mouse)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 8244.52

構造登録者

Kikuti, C.M.,Sirkia, H.,Houdusse, A. (登録日: 2022-08-16, 公開日: 2023-08-30, 最終更新日: 2024-03-13)

主引用文献

Canon, L.,Kikuti, C.,Planelles-Herrero, V.J.,Lin, T.,Mayeux, F.,Sirkia, H.,Lee, Y.I.,Heidsieck, L.,Velikovsky, L.,David, A.,Liu, X.,Moussaoui, D.,Forest, E.,Hook, P.,Petersen, K.J.,Morgan, T.E.,Di Cicco, A.,Sires-Campos, J.,Derivery, E.,Levy, D.,Delevoye, C.,Sweeney, H.L.,Houdusse, A.
How myosin VI traps its off-state, is activated and dimerizes.
Nat Commun, 14:6732-6732, 2023

PubMed Abstract: 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.

PubMed: 37872146
DOI: 10.1038/s41467-023-42376-2

実験手法

X-RAY DIFFRACTION (2.219 Å)