Cargando…

Cryo-EM structure of the inhibited (10S) form of myosin II

Myosin II is the motor protein responsible for contractility in muscle and nonmuscle cells(1). The molecule has two identical heads attached to an elongated tail, and can exist in two conformations: 10S and 6S, named for their sedimentation coefficients(2,3). The 6S conformation has an extended tail...

Descripción completa

Detalles Bibliográficos
Autores principales: Yang, Shixin, Tiwari, Prince, Lee, Kyoung Hwan, Sato, Osamu, Ikebe, Mitsuo, Padrón, Raúl, Craig, Roger
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7746622/
https://www.ncbi.nlm.nih.gov/pubmed/33268893
http://dx.doi.org/10.1038/s41586-020-3007-0
_version_ 1783624830880317440
author Yang, Shixin
Tiwari, Prince
Lee, Kyoung Hwan
Sato, Osamu
Ikebe, Mitsuo
Padrón, Raúl
Craig, Roger
author_facet Yang, Shixin
Tiwari, Prince
Lee, Kyoung Hwan
Sato, Osamu
Ikebe, Mitsuo
Padrón, Raúl
Craig, Roger
author_sort Yang, Shixin
collection PubMed
description Myosin II is the motor protein responsible for contractility in muscle and nonmuscle cells(1). The molecule has two identical heads attached to an elongated tail, and can exist in two conformations: 10S and 6S, named for their sedimentation coefficients(2,3). The 6S conformation has an extended tail and assembles into polymeric filaments, which pull on actin filaments to generate force and motion. In 10S myosin, the tail is folded into three segments and the heads bend back and interact with each other and the tail(3-7), creating a compact conformation, in which ATPase activity, actin activation and filament assembly are all highly inhibited(7,8). This switched-off structure appears to function as a key energy-conserving storage molecule in muscle and nonmuscle cells(9-12), which can be activated to form functional filaments as needed(13) – but the mechanism of its inhibition is not understood. Here we have solved the structure of smooth muscle 10S myosin to a global resolution of 4.3 Å by cryo-EM, revealing near-atomic level details of its structure for the first time. The reconstruction provides a new understanding of the head and tail regions of the molecule and of the key intramolecular contacts that cause inhibition. Our results suggest an atomic model for the off-state of myosin II, for its activation and unfolding by phosphorylation, and for understanding the clustering of disease-causing mutations near sites of intramolecular interaction.
format Online
Article
Text
id pubmed-7746622
institution National Center for Biotechnology Information
language English
publishDate 2020
record_format MEDLINE/PubMed
spelling pubmed-77466222021-06-02 Cryo-EM structure of the inhibited (10S) form of myosin II Yang, Shixin Tiwari, Prince Lee, Kyoung Hwan Sato, Osamu Ikebe, Mitsuo Padrón, Raúl Craig, Roger Nature Article Myosin II is the motor protein responsible for contractility in muscle and nonmuscle cells(1). The molecule has two identical heads attached to an elongated tail, and can exist in two conformations: 10S and 6S, named for their sedimentation coefficients(2,3). The 6S conformation has an extended tail and assembles into polymeric filaments, which pull on actin filaments to generate force and motion. In 10S myosin, the tail is folded into three segments and the heads bend back and interact with each other and the tail(3-7), creating a compact conformation, in which ATPase activity, actin activation and filament assembly are all highly inhibited(7,8). This switched-off structure appears to function as a key energy-conserving storage molecule in muscle and nonmuscle cells(9-12), which can be activated to form functional filaments as needed(13) – but the mechanism of its inhibition is not understood. Here we have solved the structure of smooth muscle 10S myosin to a global resolution of 4.3 Å by cryo-EM, revealing near-atomic level details of its structure for the first time. The reconstruction provides a new understanding of the head and tail regions of the molecule and of the key intramolecular contacts that cause inhibition. Our results suggest an atomic model for the off-state of myosin II, for its activation and unfolding by phosphorylation, and for understanding the clustering of disease-causing mutations near sites of intramolecular interaction. 2020-12-02 2020-12 /pmc/articles/PMC7746622/ /pubmed/33268893 http://dx.doi.org/10.1038/s41586-020-3007-0 Text en Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
Yang, Shixin
Tiwari, Prince
Lee, Kyoung Hwan
Sato, Osamu
Ikebe, Mitsuo
Padrón, Raúl
Craig, Roger
Cryo-EM structure of the inhibited (10S) form of myosin II
title Cryo-EM structure of the inhibited (10S) form of myosin II
title_full Cryo-EM structure of the inhibited (10S) form of myosin II
title_fullStr Cryo-EM structure of the inhibited (10S) form of myosin II
title_full_unstemmed Cryo-EM structure of the inhibited (10S) form of myosin II
title_short Cryo-EM structure of the inhibited (10S) form of myosin II
title_sort cryo-em structure of the inhibited (10s) form of myosin ii
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7746622/
https://www.ncbi.nlm.nih.gov/pubmed/33268893
http://dx.doi.org/10.1038/s41586-020-3007-0
work_keys_str_mv AT yangshixin cryoemstructureoftheinhibited10sformofmyosinii
AT tiwariprince cryoemstructureoftheinhibited10sformofmyosinii
AT leekyounghwan cryoemstructureoftheinhibited10sformofmyosinii
AT satoosamu cryoemstructureoftheinhibited10sformofmyosinii
AT ikebemitsuo cryoemstructureoftheinhibited10sformofmyosinii
AT padronraul cryoemstructureoftheinhibited10sformofmyosinii
AT craigroger cryoemstructureoftheinhibited10sformofmyosinii