Conformation of the Myosin Motor During Force Generation in Skeletal Muscle

Overview

Journal Nat Struct Biol

Specialty Cell Biology

Date 2000 Jul 6

PMID 10881196

Citations 45

Authors

M Irving

G Piazzesi

L Lucii

Y B Sun

J J Harford

I M Dobbie

M A Ferenczi

M Reconditi

V Lombardi

Affiliations

Soon will be listed here.

Abstract

Myosin motors drive muscle contraction, cytokinesis and cell locomotion, and members of the myosin superfamily have been implicated in an increasingly diverse range of cell functions. Myosin can displace a bound actin filament several nanometers in a single interaction. Crystallographic studies suggest that this 'working stroke' involves bending of the myosin head between its light chain and catalytic domains. Here we used X-ray fiber diffraction to test the crystallographic model and measure the interdomain bending during force generation in an intact single muscle fiber. The observed bending has two components: an elastic distortion and an active rotation that generates force. The average bend of the force-generating myosin heads in a muscle fiber is intermediate between those in crystal structures with different bound nucleotides, and the C-terminus of the head is displaced by 7 nm along the actin filament axis compared with the in vitro conformation seen in the absence of nucleotide.

Citing Articles

Dependence of myosin filament structure on intracellular calcium concentration in skeletal muscle.

Caremani M, Fusi L, Reconditi M, Piazzesi G, Narayanan T, Irving M J Gen Physiol. 2023; 155(12).

PMID: 37756601 PMC: 10533363. DOI: 10.1085/jgp.202313393.

Activation of the myosin motors in fast-twitch muscle of the mouse is controlled by mechano-sensing in the myosin filaments.

Hill C, Brunello E, Fusi L, Ovejero J, Irving M J Physiol. 2022; 600(17):3983-4000.

PMID: 35912434 PMC: 9544795. DOI: 10.1113/JP283048.

Muscle active force-length curve explained by an electrophysical model of interfilament spacing.

Rockenfeller R, Gunther M, Hooper S Biophys J. 2022; 121(10):1823-1855.

PMID: 35450825 PMC: 9199101. DOI: 10.1016/j.bpj.2022.04.019.

Small Angle X-ray Diffraction as a Tool for Structural Characterization of Muscle Disease.

Ma W, Irving T Int J Mol Sci. 2022; 23(6).

PMID: 35328477 PMC: 8949570. DOI: 10.3390/ijms23063052.

Myosin motors that cannot bind actin leave their folded OFF state on activation of skeletal muscle.

Reconditi M, Brunello E, Fusi L, Linari M, Lombardi V, Irving M J Gen Physiol. 2021; 153(11).

PMID: 34668926 PMC: 8532561. DOI: 10.1085/jgp.202112896.

References

Irving M, Lombardi V, Piazzesi G, Ferenczi M . Myosin head movements are synchronous with the elementary force-generating process in muscle. Nature. 1992; 357(6374):156-8. DOI: 10.1038/357156a0. View

Rayment I, Rypniewski W, Smith R, Tomchick D, Benning M, Winkelmann D . Three-dimensional structure of myosin subfragment-1: a molecular motor. Science. 1993; 261(5117):50-8. DOI: 10.1126/science.8316857. View

Wakabayashi K, Sugimoto Y, Tanaka H, Ueno Y, Takezawa Y, Amemiya Y . X-ray diffraction evidence for the extensibility of actin and myosin filaments during muscle contraction. Biophys J. 1994; 67(6):2422-35. PMC: 1225627. DOI: 10.1016/S0006-3495(94)80729-5. View

Lombardi V, Piazzesi G . The contractile response during steady lengthening of stimulated frog muscle fibres. J Physiol. 1990; 431:141-71. PMC: 1181768. DOI: 10.1113/jphysiol.1990.sp018324. View

Merritt E, Bacon D . Raster3D: photorealistic molecular graphics. Methods Enzymol. 1997; 277:505-24. DOI: 10.1016/s0076-6879(97)77028-9. View

Linari M, Dobbie I, Reconditi M, Koubassova N, Irving M, Piazzesi G . The stiffness of skeletal muscle in isometric contraction and rigor: the fraction of myosin heads bound to actin. Biophys J. 1998; 74(5):2459-73. PMC: 1299588. DOI: 10.1016/S0006-3495(98)77954-8. View

HUXLEY A, Simmons R . Proposed mechanism of force generation in striated muscle. Nature. 1971; 233(5321):533-8. DOI: 10.1038/233533a0. View

Lombardi V, Piazzesi G, Linari M . Rapid regeneration of the actin-myosin power stroke in contracting muscle. Nature. 1992; 355(6361):638-41. DOI: 10.1038/355638a0. View

Rayment I, Holden H, Whittaker M, Yohn C, Lorenz M, Holmes K . Structure of the actin-myosin complex and its implications for muscle contraction. Science. 1993; 261(5117):58-65. DOI: 10.1126/science.8316858. View

10.

Dobbie I, Linari M, Piazzesi G, Reconditi M, Koubassova N, Ferenczi M . Elastic bending and active tilting of myosin heads during muscle contraction. Nature. 1998; 396(6709):383-7. DOI: 10.1038/24647. View

11.

Huxley H, Stewart A, Sosa H, Irving T . X-ray diffraction measurements of the extensibility of actin and myosin filaments in contracting muscle. Biophys J. 1994; 67(6):2411-21. PMC: 1225626. DOI: 10.1016/S0006-3495(94)80728-3. View

12.

Corrie J, Brandmeier B, Ferguson R, Trentham D, Kendrick-Jones J, Hopkins S . Dynamic measurement of myosin light-chain-domain tilt and twist in muscle contraction. Nature. 1999; 400(6743):425-30. DOI: 10.1038/22704. View

13.

Dominguez R, Freyzon Y, Trybus K, Cohen C . Crystal structure of a vertebrate smooth muscle myosin motor domain and its complex with the essential light chain: visualization of the pre-power stroke state. Cell. 1998; 94(5):559-71. DOI: 10.1016/s0092-8674(00)81598-6. View

14.

Ford L, HUXLEY A, Simmons R . Tension responses to sudden length change in stimulated frog muscle fibres near slack length. J Physiol. 1977; 269(2):441-515. PMC: 1283722. DOI: 10.1113/jphysiol.1977.sp011911. View

15.

Houdusse A, Kalabokis V, Himmel D, Szent-Gyorgyi A, Cohen C . Atomic structure of scallop myosin subfragment S1 complexed with MgADP: a novel conformation of the myosin head. Cell. 1999; 97(4):459-70. DOI: 10.1016/s0092-8674(00)80756-4. View

16.

Lombardi V, Piazzesi G, Ferenczi M, Thirlwell H, Dobbie I, Irving M . Elastic distortion of myosin heads and repriming of the working stroke in muscle. Nature. 1995; 374(6522):553-5. DOI: 10.1038/374553a0. View

17.

Huxley H, Simmons R, Faruqi A, Kress M, BORDAS J, Koch M . Changes in the X-ray reflections from contracting muscle during rapid mechanical transients and their structural implications. J Mol Biol. 1983; 169(2):469-506. DOI: 10.1016/s0022-2836(83)80062-x. View

18.

Whittaker M, Smith J, Faust L, Milligan R, Sweeney H . A 35-A movement of smooth muscle myosin on ADP release. Nature. 1995; 378(6558):748-51. DOI: 10.1038/378748a0. View

19.

Huxley H, Faruqi A, Kress M, BORDAS J, Koch M . Time-resolved X-ray diffraction studies of the myosin layer-line reflections during muscle contraction. J Mol Biol. 1982; 158(4):637-84. DOI: 10.1016/0022-2836(82)90253-4. View

20.

Cope M, Whisstock J, Rayment I, Kendrick-Jones J . Conservation within the myosin motor domain: implications for structure and function. Structure. 1996; 4(8):969-87. DOI: 10.1016/s0969-2126(96)00103-7. View