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Title: The myosin interacting-heads motif present in live tarantula muscle explains tetanic and posttetanic phosphorylation mechanisms

Abstract

Striated muscle contraction involves sliding of actin thin filaments along myosin thick filaments, controlled by calcium through thin filament activation. In relaxed muscle, the two heads of myosin interact with each other on the filament surface to form the interacting-heads motif (IHM). A key question is how both heads are released from the surface to approach actin and produce force. Here we used time-resolved synchrotron X-ray diffraction to study tarantula muscle before and after tetani. The patterns showed that the IHM is present in live relaxed muscle. Tetanic contraction produced only a very small backbone elongation, implying that mechanosensing—proposed in vertebrate muscle—is not of primary importance in tarantula. Rather, thick filament activation results from increases in myosin phosphorylation that release a fraction of heads to produce force, with the remainder staying in the ordered IHM configuration. After the tetanus, the released heads slowly recover toward the resting, helically ordered state. During this time the released heads remain close to actin and can quickly rebind, enhancing the force produced by posttetanic twitches, structurally explaining posttetanic potentiation. Taken together, these results suggest that, in addition to stretch activation in insects, two other mechanisms for thick filament activation have evolved to disrupt themore » interactions that establish the relaxed helices of IHMs: one in invertebrates, by either regulatory light-chain phosphorylation (as in arthropods) or Ca2+-binding (in mollusks, lacking phosphorylation), and another in vertebrates, by mechanosensing.« less

Authors:
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Publication Date:
Research Org.:
Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
Sponsoring Org.:
National Institutes of Health (NIH); National Institute of General Medical Sciences (NIGMS); National Heart, Lung and Blood Institute (NHLBI); National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS); Office of Research Infrastructure Programs (ORIP); USDOE Office of Science (SC)
OSTI Identifier:
1630477
Alternate Identifier(s):
OSTI ID: 1642241
Grant/Contract Number:  
GM103622; HL139883; AR072036; AR067279; 1S10OD018090-01; AAAA-A19-119012990119-3; AC02-06CH11357
Resource Type:
Published Article
Journal Name:
Proceedings of the National Academy of Sciences of the United States of America
Additional Journal Information:
Journal Name: Proceedings of the National Academy of Sciences of the United States of America Journal Volume: 117 Journal Issue: 22; Journal ID: ISSN 0027-8424
Publisher:
National Academy of Sciences
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; skeletal muscle; thick filament activation; phosphorylation; posttetanic potentiation; myosin interacting-heads motif

Citation Formats

Padrón, Raúl, Ma, Weikang, Duno-Miranda, Sebastian, Koubassova, Natalia, Lee, Kyoung Hwan, Pinto, Antonio, Alamo, Lorenzo, Bolaños, Pura, Tsaturyan, Andrey, Irving, Thomas, and Craig, Roger. The myosin interacting-heads motif present in live tarantula muscle explains tetanic and posttetanic phosphorylation mechanisms. United States: N. p., 2020. Web. doi:10.1073/pnas.1921312117.
Padrón, Raúl, Ma, Weikang, Duno-Miranda, Sebastian, Koubassova, Natalia, Lee, Kyoung Hwan, Pinto, Antonio, Alamo, Lorenzo, Bolaños, Pura, Tsaturyan, Andrey, Irving, Thomas, & Craig, Roger. The myosin interacting-heads motif present in live tarantula muscle explains tetanic and posttetanic phosphorylation mechanisms. United States. doi:https://doi.org/10.1073/pnas.1921312117
Padrón, Raúl, Ma, Weikang, Duno-Miranda, Sebastian, Koubassova, Natalia, Lee, Kyoung Hwan, Pinto, Antonio, Alamo, Lorenzo, Bolaños, Pura, Tsaturyan, Andrey, Irving, Thomas, and Craig, Roger. Fri . "The myosin interacting-heads motif present in live tarantula muscle explains tetanic and posttetanic phosphorylation mechanisms". United States. doi:https://doi.org/10.1073/pnas.1921312117.
@article{osti_1630477,
title = {The myosin interacting-heads motif present in live tarantula muscle explains tetanic and posttetanic phosphorylation mechanisms},
author = {Padrón, Raúl and Ma, Weikang and Duno-Miranda, Sebastian and Koubassova, Natalia and Lee, Kyoung Hwan and Pinto, Antonio and Alamo, Lorenzo and Bolaños, Pura and Tsaturyan, Andrey and Irving, Thomas and Craig, Roger},
abstractNote = {Striated muscle contraction involves sliding of actin thin filaments along myosin thick filaments, controlled by calcium through thin filament activation. In relaxed muscle, the two heads of myosin interact with each other on the filament surface to form the interacting-heads motif (IHM). A key question is how both heads are released from the surface to approach actin and produce force. Here we used time-resolved synchrotron X-ray diffraction to study tarantula muscle before and after tetani. The patterns showed that the IHM is present in live relaxed muscle. Tetanic contraction produced only a very small backbone elongation, implying that mechanosensing—proposed in vertebrate muscle—is not of primary importance in tarantula. Rather, thick filament activation results from increases in myosin phosphorylation that release a fraction of heads to produce force, with the remainder staying in the ordered IHM configuration. After the tetanus, the released heads slowly recover toward the resting, helically ordered state. During this time the released heads remain close to actin and can quickly rebind, enhancing the force produced by posttetanic twitches, structurally explaining posttetanic potentiation. Taken together, these results suggest that, in addition to stretch activation in insects, two other mechanisms for thick filament activation have evolved to disrupt the interactions that establish the relaxed helices of IHMs: one in invertebrates, by either regulatory light-chain phosphorylation (as in arthropods) or Ca2+-binding (in mollusks, lacking phosphorylation), and another in vertebrates, by mechanosensing.},
doi = {10.1073/pnas.1921312117},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
number = 22,
volume = 117,
place = {United States},
year = {2020},
month = {5}
}

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DOI: https://doi.org/10.1073/pnas.1921312117

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