Homologous mutations in human β, embryonic, and perinatal muscle myosins have divergent effects on molecular power generation
Abstract
Mutations at a highly conserved homologous residue in three closely related muscle myosins cause three distinct diseases involving muscle defects: R671C in β-cardiac myosin causes hypertrophic cardiomyopathy, R672C and R672H in embryonic skeletal myosin cause Freeman–Sheldon syndrome, and R674Q in perinatal skeletal myosin causes trismus-pseudocamptodactyly syndrome. It is not known whether their effects at the molecular level are similar to one another or correlate with disease phenotype and severity. To this end, we investigated the effects of the homologous mutations on key factors of molecular power production using recombinantly expressed human β, embryonic, and perinatal myosin subfragment-1. We found large effects in the developmental myosins but minimal effects in β myosin, and magnitude of changes correlated partially with clinical severity. The mutations in the developmental myosins dramatically decreased the step size and load-sensitive actin-detachment rate of single molecules measured by optical tweezers, in addition to decreasing overall enzymatic (ATPase) cycle rate. In contrast, the only measured effect of R671C in β myosin was a larger step size. Our measurements of step size and bound times predicted velocities consistent with those measured in an in vitro motility assay. Finally, molecular dynamics simulations predicted that the arginine to cysteine mutation in embryonic,more »
- Authors:
-
- Department of Biochemistry, Stanford University School of Medicine, Stanford, CA 94305, Stanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA 94305, Biosciences and Biotechnology Division, Lawrence Livermore National Laboratory, Livermore, CA 94550
- BioFrontiers Institute, University of Colorado Boulder, Boulder, CO 80309, Department of Molecular, Cellular, and Developmental Biology, University of Colorado Boulder, Boulder, CO 80309, Kainomyx, Inc., Palo Alto, CA 94304
- Department of Biochemistry and Biophysics, Washington University in St. Louis, St. Louis, MO 63110, Medical Scientist Training Program, Washington University in St. Louis, St. Louis, MO 63110
- Department of Biochemistry and Biophysics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104
- Department of Biochemistry, Stanford University School of Medicine, Stanford, CA 94305, Stanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA 94305, Kainomyx, Inc., Palo Alto, CA 94304
- BioFrontiers Institute, University of Colorado Boulder, Boulder, CO 80309, Department of Molecular, Cellular, and Developmental Biology, University of Colorado Boulder, Boulder, CO 80309
- Publication Date:
- Sponsoring Org.:
- USDOE
- OSTI Identifier:
- 2309805
- Grant/Contract Number:
- postdoc career fund
- 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: 121 Journal Issue: 9; Journal ID: ISSN 0027-8424
- Publisher:
- Proceedings of the National Academy of Sciences
- Country of Publication:
- United States
- Language:
- English
Citation Formats
Liu, Chao, Karabina, Anastasia, Meller, Artur, Bhattacharjee, Ayan, Agostino, Colby J., Bowman, Greg R., Ruppel, Kathleen M., Spudich, James A., and Leinwand, Leslie A. Homologous mutations in human β, embryonic, and perinatal muscle myosins have divergent effects on molecular power generation. United States: N. p., 2024.
Web. doi:10.1073/pnas.2315472121.
Liu, Chao, Karabina, Anastasia, Meller, Artur, Bhattacharjee, Ayan, Agostino, Colby J., Bowman, Greg R., Ruppel, Kathleen M., Spudich, James A., & Leinwand, Leslie A. Homologous mutations in human β, embryonic, and perinatal muscle myosins have divergent effects on molecular power generation. United States. https://doi.org/10.1073/pnas.2315472121
Liu, Chao, Karabina, Anastasia, Meller, Artur, Bhattacharjee, Ayan, Agostino, Colby J., Bowman, Greg R., Ruppel, Kathleen M., Spudich, James A., and Leinwand, Leslie A. Tue .
"Homologous mutations in human β, embryonic, and perinatal muscle myosins have divergent effects on molecular power generation". United States. https://doi.org/10.1073/pnas.2315472121.
@article{osti_2309805,
title = {Homologous mutations in human β, embryonic, and perinatal muscle myosins have divergent effects on molecular power generation},
author = {Liu, Chao and Karabina, Anastasia and Meller, Artur and Bhattacharjee, Ayan and Agostino, Colby J. and Bowman, Greg R. and Ruppel, Kathleen M. and Spudich, James A. and Leinwand, Leslie A.},
abstractNote = {Mutations at a highly conserved homologous residue in three closely related muscle myosins cause three distinct diseases involving muscle defects: R671C in β-cardiac myosin causes hypertrophic cardiomyopathy, R672C and R672H in embryonic skeletal myosin cause Freeman–Sheldon syndrome, and R674Q in perinatal skeletal myosin causes trismus-pseudocamptodactyly syndrome. It is not known whether their effects at the molecular level are similar to one another or correlate with disease phenotype and severity. To this end, we investigated the effects of the homologous mutations on key factors of molecular power production using recombinantly expressed human β, embryonic, and perinatal myosin subfragment-1. We found large effects in the developmental myosins but minimal effects in β myosin, and magnitude of changes correlated partially with clinical severity. The mutations in the developmental myosins dramatically decreased the step size and load-sensitive actin-detachment rate of single molecules measured by optical tweezers, in addition to decreasing overall enzymatic (ATPase) cycle rate. In contrast, the only measured effect of R671C in β myosin was a larger step size. Our measurements of step size and bound times predicted velocities consistent with those measured in an in vitro motility assay. Finally, molecular dynamics simulations predicted that the arginine to cysteine mutation in embryonic, but not β, myosin may reduce pre-powerstroke lever arm priming and ADP pocket opening, providing a possible structural mechanism consistent with the experimental observations. This paper presents direct comparisons of homologous mutations in several different myosin isoforms, whose divergent functional effects are a testament to myosin’s highly allosteric nature.},
doi = {10.1073/pnas.2315472121},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
number = 9,
volume = 121,
place = {United States},
year = {Tue Feb 20 00:00:00 EST 2024},
month = {Tue Feb 20 00:00:00 EST 2024}
}
https://doi.org/10.1073/pnas.2315472121
Works referenced in this record:
Fluorescent actin filaments move on myosin fixed to a glass surface.
journal, September 1986
- Kron, S. J.; Spudich, J. A.
- Proceedings of the National Academy of Sciences, Vol. 83, Issue 17
Contractility and kinetics of human fetal and human adult skeletal muscle
journal, June 2013
- Racca, Alice W.; Beck, Anita E.; Rao, Vijay S.
- The Journal of Physiology, Vol. 591, Issue 12
Structural basis for drug-induced allosteric changes to human β-cardiac myosin motor activity
journal, August 2015
- Winkelmann, Donald A.; Forgacs, Eva; Miller, Matthew T.
- Nature Communications, Vol. 6, Issue 1
Transgenic Mouse α- and β-Cardiac Myosins Containing the R403Q Mutation Show Isoform-dependent Transient Kinetic Differences
journal, May 2013
- Lowey, Susan; Bretton, Vera; Gulick, James
- Journal of Biological Chemistry, Vol. 288, Issue 21
Harmonic force spectroscopy measures load-dependent kinetics of individual human β-cardiac myosin molecules
journal, August 2015
- Sung, Jongmin; Nag, Suman; Mortensen, Kim I.
- Nature Communications, Vol. 6, Issue 1
Myosin cleft closure determines the energetics of the actomyosin interaction
journal, September 2010
- Takács, Balázs; O'Neall‐Hennessey, Elizabeth; Hetényi, Csaba
- The FASEB Journal, Vol. 25, Issue 1
Hypertrophic cardiomyopathy mutations in the pliant and light chain-binding regions of the lever arm of human β-cardiac myosin have divergent effects on myosin function
journal, June 2022
- Morck, Makenna M.; Bhowmik, Debanjan; Pathak, Divya
- eLife, Vol. 11
Positive cardiac inotrope omecamtiv mecarbil activates muscle despite suppressing the myosin working stroke
journal, September 2018
- Woody, Michael S.; Greenberg, Michael J.; Barua, Bipasha
- Nature Communications, Vol. 9, Issue 1
ADP dissociation from actomyosin subfragment 1 is sufficiently slow to limit the unloaded shortening velocity in vertebrate muscle.
journal, February 1985
- Siemankowski, R. F.; Wiseman, M. O.; White, H. D.
- Proceedings of the National Academy of Sciences, Vol. 82, Issue 3
How to Measure Load-Dependent Kinetics of Individual Motor Molecules Without a Force-Clamp
book, October 2016
- Sung, J.; Mortensen, K. I.; Spudich, J. A.
- Methods in Enzymology
Myosin with hypertrophic cardiac mutation R712L has a decreased working stroke which is rescued by omecamtiv mecarbil
journal, February 2021
- Snoberger, Aaron; Barua, Bipasha; Atherton, Jennifer L.
- eLife, Vol. 10
Ensemble Force Changes that Result from Human Cardiac Myosin Mutations and a Small-Molecule Effector
journal, May 2015
- Aksel, Tural; Choe Yu, Elizabeth; Sutton, Shirley
- Cell Reports, Vol. 11, Issue 6
Myosin step size
journal, August 1990
- Uyeda, Taro Q. P.; Kron, Stephen J.; Spudich, James A.
- Journal of Molecular Biology, Vol. 214, Issue 3
Sudden Deaths in Young Competitive Athletes
journal, March 2009
- Maron, Barry J.; Doerer, Joseph J.; Haas, Tammy S.
- Circulation, Vol. 119, Issue 8
Mavacamten for treatment of symptomatic obstructive hypertrophic cardiomyopathy (EXPLORER-HCM): health status analysis of a randomised, double-blind, placebo-controlled, phase 3 trial
journal, June 2021
- Spertus, John A.; Fine, Jennifer T.; Elliott, Perry
- The Lancet, Vol. 397, Issue 10293
Mutations in embryonic myosin heavy chain (MYH3) cause Freeman-Sheldon syndrome and Sheldon-Hall syndrome
journal, April 2006
- Toydemir, Reha M.; Rutherford, Ann; Whitby, Frank G.
- Nature Genetics, Vol. 38, Issue 5
Developmental myosins: expression patterns and functional significance
journal, July 2015
- Schiaffino, Stefano; Rossi, Alberto C.; Smerdu, Vika
- Skeletal Muscle, Vol. 5, Issue 1
Clinical Characteristics and Natural History of Freeman-Sheldon Syndrome
journal, March 2006
- Stevenson, David A.; Carey, John C.; Palumbos, Janice
- Pediatrics, Vol. 117, Issue 3
Kinetics of the interaction between actin, ADP, and cardiac myosin-S1.
journal, April 1984
- Siemankowski, R. F.; White, H. D.
- Journal of Biological Chemistry, Vol. 259, Issue 8
Molecular consequences of the R453C hypertrophic cardiomyopathy mutation on human -cardiac myosin motor function
journal, June 2013
- Sommese, R. F.; Sung, J.; Nag, S.
- Proceedings of the National Academy of Sciences, Vol. 110, Issue 31
A mixed-kinetic model describes unloaded velocities of smooth, skeletal, and cardiac muscle myosin filaments in vitro
journal, December 2017
- Brizendine, Richard K.; Sheehy, Gabriel G.; Alcala, Diego B.
- Science Advances, Vol. 3, Issue 12
Comparison of simple potential functions for simulating liquid water
journal, July 1983
- Jorgensen, William L.; Chandrasekhar, Jayaraman; Madura, Jeffry D.
- The Journal of Chemical Physics, Vol. 79, Issue 2
Genotype‐phenotype relationships in Freeman–Sheldon syndrome
journal, September 2014
- Beck, Anita E.; McMillin, Margaret J.; Gildersleeve, Heidi I. S.
- American Journal of Medical Genetics Part A, Vol. 164, Issue 11
What Limits the Velocity of Fast-skeletal Muscle Contraction in Mammals?
journal, January 2006
- Nyitrai, Miklós; Rossi, Rosetta; Adamek, Nancy
- Journal of Molecular Biology, Vol. 355, Issue 3
Inherent Force-Dependent Properties of β -Cardiac Myosin Contribute to the Force-Velocity Relationship of Cardiac Muscle
journal, December 2014
- Greenberg, Michael J.; Shuman, Henry; Ostap, E. Michael
- Biophysical Journal, Vol. 107, Issue 12
Myosin Heavy Chains IIa and IId Are Functionally Distinct in the Mouse
journal, May 1998
- Sartorius, Carol A.; Lu, Brian D.; Acakpo-Satchivi, Leslie
- The Journal of Cell Biology, Vol. 141, Issue 4
Reductions in ATPase activity, actin sliding velocity, and myofibril stability yield muscle dysfunction in Drosophila models of myosin-based Freeman–Sheldon syndrome
journal, January 2019
- Rao, Deepti S.; Kronert, William A.; Guo, Yiming
- Molecular Biology of the Cell, Vol. 30, Issue 1
GROMACS: High performance molecular simulations through multi-level parallelism from laptops to supercomputers
journal, September 2015
- Abraham, Mark James; Murtola, Teemu; Schulz, Roland
- SoftwareX, Vol. 1-2
The ATPase cycle of human muscle myosin II isoforms: Adaptation of a single mechanochemical cycle for different physiological roles
journal, September 2019
- Johnson, Chloe A.; Walklate, Jonathan; Svicevic, Marina
- Journal of Biological Chemistry, Vol. 294, Issue 39
Myosin heavy chain mutations that cause Freeman-Sheldon syndrome lead to muscle structural and functional defects in Drosophila
journal, May 2019
- Das, Shreyasi; Kumar, Pankaj; Verma, Aakanksha
- Developmental Biology, Vol. 449, Issue 2
Early-Onset Hypertrophic Cardiomyopathy Mutations Significantly Increase the Velocity, Force, and Actin-Activated ATPase Activity of Human β-Cardiac Myosin
journal, December 2016
- Adhikari, Arjun S.; Kooiker, Kristina B.; Sarkar, Saswata S.
- Cell Reports, Vol. 17, Issue 11
Contractility parameters of human β-cardiac myosin with the hypertrophic cardiomyopathy mutation R403Q show loss of motor function
journal, October 2015
- Nag, Suman; Sommese, Ruth F.; Ujfalusi, Zoltan
- Science Advances, Vol. 1, Issue 9
Single molecule mechanics resolves the earliest events in force generation by cardiac myosin
journal, September 2019
- Woody, Michael S.; Winkelmann, Donald A.; Capitanio, Marco
- eLife, Vol. 8
Unc45b Forms a Cytosolic Complex with Hsp90 and Targets the Unfolded Myosin Motor Domain
journal, May 2008
- Srikakulam, Rajani; Liu, Li; Winkelmann, Donald A.
- PLoS ONE, Vol. 3, Issue 5
The motor protein myosin-I produces its working stroke in two steps
journal, April 1999
- Veigel, Claudia; Coluccio, Lynne M.; Jontes, James D.
- Nature, Vol. 398, Issue 6727
Hereditary myosin myopathies
journal, May 2007
- Oldfors, Anders
- Neuromuscular Disorders, Vol. 17, Issue 5
Mutation of Perinatal Myosin Heavy Chain Associated with a Carney Complex Variant
journal, July 2004
- Veugelers, Mark; Bressan, Michael; McDermott, Deborah A.
- New England Journal of Medicine, Vol. 351, Issue 5
Dilated cardiomyopathy mutation in the converter domain of human cardiac myosin alters motor activity and response to omecamtiv mecarbil
journal, November 2019
- Tang, Wanjian; Unrath, William C.; Desetty, Rohini
- Journal of Biological Chemistry, Vol. 294, Issue 46
CHARMM36m: an improved force field for folded and intrinsically disordered proteins
journal, November 2016
- Huang, Jing; Rauscher, Sarah; Nawrocki, Grzegorz
- Nature Methods, Vol. 14, Issue 1
Postnatal Myosin Heavy Chain Isoform Expression in Normal Mice and Mice Null for IIb or IId Myosin Heavy Chains
journal, January 2001
- Allen, David L.; Leinwand, Leslie A.
- Developmental Biology, Vol. 229, Issue 2
2-Deoxy-ATP Enhances Contractility of Rat Cardiac Muscle
journal, June 2000
- Regnier, M.; Rivera, A. J.; Chen, Y.
- Circulation Research, Vol. 86, Issue 12
Hypertrophic cardiomyopathy
journal, January 2013
- Maron, Barry J.; Maron, Martin S.
- The Lancet, Vol. 381, Issue 9862
MDTraj: A Modern Open Library for the Analysis of Molecular Dynamics Trajectories
journal, October 2015
- McGibbon, Robert T.; Beauchamp, Kyle A.; Harrigan, Matthew P.
- Biophysical Journal, Vol. 109, Issue 8
Myosinopathies: pathology and mechanisms
journal, August 2012
- Tajsharghi, Homa; Oldfors, Anders
- Acta Neuropathologica, Vol. 125, Issue 1
Growth and Muscle Defects in Mice Lacking Adult Myosin Heavy Chain Genes
journal, December 1997
- Acakpo-Satchivi, Leslie J. R.; Edelmann, Winfried; Sartorius, Carol
- The Journal of Cell Biology, Vol. 139, Issue 5
Identification of functional differences between recombinant human α and β cardiac myosin motors
journal, February 2012
- Deacon, John C.; Bloemink, Marieke J.; Rezavandi, Heresh
- Cellular and Molecular Life Sciences, Vol. 69, Issue 13
Structural and Functional Insights into the Myosin Motor Mechanism
journal, April 2010
- Sweeney, H. Lee; Houdusse, Anne
- Annual Review of Biophysics, Vol. 39, Issue 1
Mutations in the motor domain modulate myosin activity and myofibril organization
journal, October 2003
- Wang, Qun; Moncman, Carole L.; Winkelmann, Donald A.
- Journal of Cell Science, Vol. 116, Issue 20
Arthrogryposis: A Review and Update
journal, July 2009
- Bamshad, Michael; Van Heest, Ann E.; Pleasure, David
- Journal of Bone and Joint Surgery, Vol. 91, Issue Supplement_4
Comparative Protein Modelling by Satisfaction of Spatial Restraints
journal, December 1993
- Šali, Andrej; Blundell, Tom L.
- Journal of Molecular Biology, Vol. 234, Issue 3
The hypertrophic cardiomyopathy mutations R403Q and R663H increase the number of myosin heads available to interact with actin
journal, April 2020
- Sarkar, Saswata S.; Trivedi, Darshan V.; Morck, Makenna M.
- Science Advances, Vol. 6, Issue 14
Mechanism of Blebbistatin Inhibition of Myosin II
journal, June 2004
- Kovács, Mihály; Tóth, Judit; Hetényi, Csaba
- Journal of Biological Chemistry, Vol. 279, Issue 34
Canonical sampling through velocity rescaling
journal, January 2007
- Bussi, Giovanni; Donadio, Davide; Parrinello, Michele
- The Journal of Chemical Physics, Vol. 126, Issue 1
New Perspectives on the Prevalence of Hypertrophic Cardiomyopathy
journal, March 2015
- Semsarian, Christopher; Ingles, Jodie; Maron, Martin S.
- Journal of the American College of Cardiology, Vol. 65, Issue 12
Prevalence of Hypertrophic Cardiomyopathy in a General Population of Young Adults: Echocardiographic Analysis of 4111 Subjects in the CARDIA Study
journal, August 1995
- Maron, Barry J.; Gardin, Julius M.; Flack, John M.
- Circulation, Vol. 92, Issue 4
Functional divergence of the sarcomeric myosin, MYH7b, supports species-specific biological roles
journal, January 2023
- Lee, Lindsey A.; Barrick, Samantha K.; Meller, Artur
- Journal of Biological Chemistry, Vol. 299, Issue 1
Functional Effects of the Hypertrophic Cardiomyopathy R403Q Mutation Are Different in an α- or β-Myosin Heavy Chain Backbone
journal, July 2008
- Lowey, Susan; Lesko, Leanne M.; Rovner, Arthur S.
- Journal of Biological Chemistry, Vol. 283, Issue 29
Cardiac Myosin Activation with Omecamtiv Mecarbil in Systolic Heart Failure
journal, January 2021
- Teerlink, John R.; Diaz, Rafael; Felker, G. Michael
- New England Journal of Medicine, Vol. 384, Issue 2
Molecular dynamics with coupling to an external bath
journal, October 1984
- Berendsen, H. J. C.; Postma, J. P. M.; van Gunsteren, W. F.
- The Journal of Chemical Physics, Vol. 81, Issue 8
The embryonic myosin R672C mutation that underlies Freeman-Sheldon syndrome impairs cross-bridge detachment and cycling in adult skeletal muscle
journal, March 2015
- Racca, A. W.; Beck, A. E.; McMillin, M. J.
- Human Molecular Genetics, Vol. 24, Issue 12
Mavacamten stabilizes an autoinhibited state of two-headed cardiac myosin
journal, July 2018
- Rohde, John A.; Roopnarine, Osha; Thomas, David D.
- Proceedings of the National Academy of Sciences, Vol. 115, Issue 32
Mechanical Coupling between Myosin Molecules Causes Differences between Ensemble and Single-Molecule Measurements
journal, August 2012
- Walcott, Sam; Warshaw, David M.; Debold, Edward P.
- Biophysical Journal, Vol. 103, Issue 3
Controlling load-dependent kinetics of β-cardiac myosin at the single-molecule level
journal, June 2018
- Liu, Chao; Kawana, Masataka; Song, Dan
- Nature Structural & Molecular Biology, Vol. 25, Issue 6
Effects of myosin variants on interacting-heads motif explain distinct hypertrophic and dilated cardiomyopathy phenotypes
journal, June 2017
- Alamo, Lorenzo; Ware, James S.; Pinto, Antonio
- eLife, Vol. 6
Hypertrophic cardiomyopathy β-cardiac myosin mutation (P710R) leads to hypercontractility by disrupting super relaxed state
journal, June 2021
- Vander Roest, Alison Schroer; Liu, Chao; Morck, Makenna M.
- Proceedings of the National Academy of Sciences, Vol. 118, Issue 24
A Peptide Tag System for Facile Purification and Single-Molecule Immobilization
journal, November 2009
- Huang, Jin; Nagy, Stanislav S.; Koide, Akiko
- Biochemistry, Vol. 48, Issue 50
Conformational distributions of isolated myosin motor domains encode their mechanochemical properties
journal, May 2020
- Porter, Justin R.; Meller, Artur; Zimmerman, Maxwell I.
- eLife, Vol. 9
Polymorphic transitions in single crystals: A new molecular dynamics method
journal, December 1981
- Parrinello, M.; Rahman, A.
- Journal of Applied Physics, Vol. 52, Issue 12
Biophysical properties of human β-cardiac myosin with converter mutations that cause hypertrophic cardiomyopathy
journal, February 2017
- Kawana, Masataka; Sarkar, Saswata S.; Sutton, Shirley
- Science Advances, Vol. 3, Issue 2
Chapter 6 Kinetic and Equilibrium Analysis of the Myosin ATPase
book, March 2009
- De La Cruz, Enrique M.; Michael Ostap, E.
- Methods in Enzymology
Whole‑exome sequencing reveals MYH7 p.R671C mutation in three different phenotypes of familial hypertrophic cardiomyopathy
journal, July 2021
- Yu, Wei; Huang, Mi-Mi; Zhang, Guo-Hong
- Experimental and Therapeutic Medicine, Vol. 22, Issue 3
Freeman-Burian syndrome
journal, January 2019
- Poling, Mikaela I.; Dufresne, Craig R.; Chamberlain, Robert L.
- Orphanet Journal of Rare Diseases, Vol. 14, Issue 1
Phenotypic variation in trismus-pseudocamptodactyly syndrome caused by a recurrent MYH8 mutation
journal, January 2008
- Minzer-Conzetti, Karen; Wu, Erica; Vargervik, Karin
- Clinical Dysmorphology, Vol. 17, Issue 1
Deciphering the super relaxed state of human β-cardiac myosin and the mode of action of mavacamten from myosin molecules to muscle fibers
journal, August 2018
- Anderson, Robert L.; Trivedi, Darshan V.; Sarkar, Saswata S.
- Proceedings of the National Academy of Sciences, Vol. 115, Issue 35
Trismus‐pseudocamptodactyly syndrome is caused by recurrent mutation of MYH8
journal, October 2006
- Toydemir, Reha M.; Chen, Harold; Proud, Virginia K.
- American Journal of Medical Genetics Part A, Vol. 140A, Issue 22
Modeling the Actin.myosin ATPase Cross-Bridge Cycle for Skeletal and Cardiac Muscle Myosin Isoforms
journal, March 2017
- Mijailovich, Srbolujub M.; Nedic, Djordje; Svicevic, Marina
- Biophysical Journal, Vol. 112, Issue 5
Hypertrophic cardiomyopathy: Mutations to mechanisms to therapies
journal, September 2022
- Kawana, Masataka; Spudich, James A.; Ruppel, Kathleen M.
- Frontiers in Physiology, Vol. 13
Motility Assay to Probe the Calcium Sensitivity of Myosin and Regulated Thin Filaments
book, December 2023
- Liu, Chao; Ruppel, Kathleen M.; Spudich, James A.
- Familial Cardiomyopathies
The myosin mesa and the basis of hypercontractility caused by hypertrophic cardiomyopathy mutations
journal, May 2017
- Nag, Suman; Trivedi, Darshan V.; Sarkar, Saswata S.
- Nature Structural & Molecular Biology, Vol. 24, Issue 6
Pi Release from Myosin: A Simulation Analysis of Possible Pathways
journal, March 2010
- Cecchini, Marco; Alexeev, Yuri; Karplus, Martin
- Structure, Vol. 18, Issue 4
Modelling proteins’ hidden conformations to predict antibiotic resistance
journal, October 2016
- Hart, Kathryn M.; Ho, Chris M. W.; Dutta, Supratik
- Nature Communications, Vol. 7, Issue 1
Prolonged myosin binding increases muscle stiffness in Drosophila models of Freeman-Sheldon syndrome
journal, March 2021
- Bell, Kaylyn M.; Huang, Alice; Kronert, William A.
- Biophysical Journal, Vol. 120, Issue 5
Deep learning the structural determinants of protein biochemical properties by comparing structural ensembles with DiffNets
journal, May 2021
- Ward, Michael D.; Zimmerman, Maxwell I.; Meller, Artur
- Nature Communications, Vol. 12, Issue 1
Drug specificity and affinity are encoded in the probability of cryptic pocket opening in myosin motor domains
journal, January 2023
- Meller, Artur; Lotthammer, Jeffrey M.; Smith, Louis G.
- eLife, Vol. 12
Load-dependent kinetics of force production by smooth muscle myosin measured with optical tweezers
journal, October 2003
- Veigel, Claudia; Molloy, Justin E.; Schmitz, Stephan
- Nature Cell Biology, Vol. 5, Issue 11
The Mammalian Myosin Heavy Chain gene Family
journal, November 1996
- Weiss, Allison; Leinwand, Leslie A.
- Annual Review of Cell and Developmental Biology, Vol. 12, Issue 1
Magnesium Ion–Water Coordination and Exchange in Biomolecular Simulations
journal, March 2012
- Allnér, Olof; Nilsson, Lennart; Villa, Alessandra
- Journal of Chemical Theory and Computation, Vol. 8, Issue 4
Functional diversity among a family of human skeletal muscle myosin motors
journal, December 2009
- Resnicow, Daniel I.; Deacon, John C.; Warrick, Hans M.
- Proceedings of the National Academy of Sciences, Vol. 107, Issue 3
The Most Prevalent Freeman-Sheldon Syndrome Mutations in the Embryonic Myosin Motor Share Functional Defects
journal, March 2016
- Walklate, Jonathan; Vera, Carlos; Bloemink, Marieke J.
- Journal of Biological Chemistry, Vol. 291, Issue 19