Alternative N-terminal Regions of Myosin Heavy Chain II Regulate Communication of the Purine Binding Loop with the Essential Light Chain

Overview

Journal J Biol Chem

Specialty Biochemistry

Date 2020 Aug 21

PMID 32817166

Citations 4

Authors

Marieke J Bloemink

Karen H Hsu

Michael A Geeves

Sanford I Bernstein

Affiliations

Soon will be listed here.

Abstract

We investigated the biochemical and biophysical properties of one of the four alternative exon-encoded regions within the myosin catalytic domain. This region is encoded by alternative exons 3a and 3b and includes part of the N-terminal β-barrel. Chimeric myosin constructs (IFI-3a and EMB-3b) were generated by exchanging the exon 3-encoded areas between native slow embryonic body wall (EMB) and fast indirect flight muscle myosin isoforms (IFI). We found that this exchange alters the kinetic properties of the myosin S1 head. The ADP release rate ( ) in the absence of actin is completely reversed for each chimera compared with the native isoforms. Steady-state data also suggest a reciprocal shift, with basal and actin-activated ATPase activity of IFI-3a showing reduced values compared with wild-type (WT) IFI, whereas for EMB-3b these values are increased compared with wild-type (WT) EMB. In the presence of actin, ADP affinity ( ) is unchanged for IFI-3a, compared with IFI, but ADP affinity for EMB-3b is increased, compared with EMB, and shifted toward IFI values. ATP-induced dissociation of acto-S1 ( ) is reduced for both exon 3 chimeras. Homology modeling, combined with a recently reported crystal structure for EMB, indicates that the exon 3-encoded region in the myosin head is part of the communication pathway between the nucleotide binding pocket (purine binding loop) and the essential light chain, emphasizing an important role for this variable N-terminal domain in regulating actomyosin crossbridge kinetics, in particular with respect to the force-sensing properties of myosin isoforms.

Citing Articles

Azobenzene-Based Photoswitchable Substrates for Advanced Mechanistic Studies of Model Haloalkane Dehalogenase Enzyme Family.

Slanska M, Stackova L, Marques S, Stacko P, Martinek M, Jilek L ACS Catal. 2024; 14(15):11635-11645.

PMID: 39114093 PMC: 11301625. DOI: 10.1021/acscatal.4c03503.

Aging-affiliated post-translational modifications of skeletal muscle myosin affect biochemical properties, myofibril structure, muscle function, and proteostasis.

Neal C, Kronert W, Camillo J, Suggs J, Huxford T, Bernstein S Aging Cell. 2024; 23(6):e14134.

PMID: 38506610 PMC: 11296117. DOI: 10.1111/acel.14134.

High-resolution structures of the actomyosin-V complex in three nucleotide states provide insights into the force generation mechanism.

Pospich S, Sweeney H, Houdusse A, Raunser S Elife. 2021; 10.

PMID: 34812732 PMC: 8735999. DOI: 10.7554/eLife.73724.

Alpha and beta myosin isoforms and human atrial and ventricular contraction.

Walklate J, Ferrantini C, Johnson C, Tesi C, Poggesi C, Geeves M Cell Mol Life Sci. 2021; 78(23):7309-7337.

PMID: 34704115 PMC: 8629898. DOI: 10.1007/s00018-021-03971-y.

References

Bloemink M, Dambacher C, Knowles A, Melkani G, Geeves M, Bernstein S . Alternative exon 9-encoded relay domains affect more than one communication pathway in the Drosophila myosin head. J Mol Biol. 2009; 389(4):707-21. PMC: 3119900. DOI: 10.1016/j.jmb.2009.04.036. View

Robert-Paganin J, Auguin D, Houdusse A . Hypertrophic cardiomyopathy disease results from disparate impairments of cardiac myosin function and auto-inhibition. Nat Commun. 2018; 9(1):4019. PMC: 6167380. DOI: 10.1038/s41467-018-06191-4. View

Shuman H, Greenberg M, Zwolak A, Lin T, Sindelar C, Dominguez R . A vertebrate myosin-I structure reveals unique insights into myosin mechanochemical tuning. Proc Natl Acad Sci U S A. 2014; 111(6):2116-21. PMC: 3926069. DOI: 10.1073/pnas.1321022111. View

Schmid S, Hugel T . Controlling protein function by fine-tuning conformational flexibility. Elife. 2020; 9. PMC: 7375816. DOI: 10.7554/eLife.57180. View

Swank D, Kronert W, Bernstein S, Maughan D . Alternative N-terminal regions of Drosophila myosin heavy chain tune muscle kinetics for optimal power output. Biophys J. 2004; 87(3):1805-14. PMC: 1304585. DOI: 10.1529/biophysj.103.032078. View

Schwede T, Kopp J, Guex N, Peitsch M . SWISS-MODEL: An automated protein homology-modeling server. Nucleic Acids Res. 2003; 31(13):3381-5. PMC: 168927. DOI: 10.1093/nar/gkg520. View

Arnold K, Bordoli L, Kopp J, Schwede T . The SWISS-MODEL workspace: a web-based environment for protein structure homology modelling. Bioinformatics. 2005; 22(2):195-201. DOI: 10.1093/bioinformatics/bti770. View

Colegrave M, Peckham M . Structural implications of β-cardiac myosin heavy chain mutations in human disease. Anat Rec (Hoboken). 2014; 297(9):1670-80. DOI: 10.1002/ar.22973. View

Greenberg M, Lin T, Shuman H, Ostap E . Mechanochemical tuning of myosin-I by the N-terminal region. Proc Natl Acad Sci U S A. 2015; 112(26):E3337-44. PMC: 4491760. DOI: 10.1073/pnas.1506633112. View

10.

Weiss S, Chizhov I, Geeves M . A flash photolysis fluorescence/light scattering apparatus for use with sub microgram quantities of muscle proteins. J Muscle Res Cell Motil. 2000; 21(5):423-32. DOI: 10.1023/a:1005690106951. View

11.

Lowey S, Saraswat L, Liu H, Volkmann N, Hanein D . Evidence for an interaction between the SH3 domain and the N-terminal extension of the essential light chain in class II myosins. J Mol Biol. 2007; 371(4):902-13. PMC: 2693010. DOI: 10.1016/j.jmb.2007.05.080. View

12.

Miller B, Nyitrai M, Bernstein S, Geeves M . Kinetic analysis of Drosophila muscle myosin isoforms suggests a novel mode of mechanochemical coupling. J Biol Chem. 2003; 278(50):50293-300. DOI: 10.1074/jbc.M308318200. View

13.

Nanasi P, Komaromi I, Gaburjakova M, Almassy J . Omecamtiv Mecarbil: A Myosin Motor Activator Agent with Promising Clinical Performance and New in vitro Results. Curr Med Chem. 2017; 25(15):1720-1728. DOI: 10.2174/0929867325666171222164320. View

14.

George E, Ober M, EMERSON Jr C . Functional domains of the Drosophila melanogaster muscle myosin heavy-chain gene are encoded by alternatively spliced exons. Mol Cell Biol. 1989; 9(7):2957-74. PMC: 362764. DOI: 10.1128/mcb.9.7.2957-2974.1989. View

15.

Silva R, Sparrow J, Geeves M . Isolation and kinetic characterisation of myosin and myosin S1 from the Drosophila indirect flight muscles. J Muscle Res Cell Motil. 2004; 24(8):489-98. DOI: 10.1023/b:jure.0000009809.69829.74. View

16.

Yang C, Kaplan C, Thatcher M, Swank D . The influence of myosin converter and relay domains on cross-bridge kinetics of Drosophila indirect flight muscle. Biophys J. 2010; 99(5):1546-55. PMC: 2931743. DOI: 10.1016/j.bpj.2010.06.047. View

17.

Webb M, Corrie J . Fluorescent coumarin-labeled nucleotides to measure ADP release from actomyosin. Biophys J. 2001; 81(3):1562-9. PMC: 1301634. DOI: 10.1016/S0006-3495(01)75810-9. View

18.

Nyitrai M, Rossi R, Adamek N, Pellegrino M, Bottinelli R, Geeves M . What limits the velocity of fast-skeletal muscle contraction in mammals?. J Mol Biol. 2005; 355(3):432-42. DOI: 10.1016/j.jmb.2005.10.063. View

19.

Wells L, Edwards K, Bernstein S . Myosin heavy chain isoforms regulate muscle function but not myofibril assembly. EMBO J. 1996; 15(17):4454-9. PMC: 452174. View

20.

Poetter K, Jiang H, Hassanzadeh S, Master S, Chang A, Dalakas M . Mutations in either the essential or regulatory light chains of myosin are associated with a rare myopathy in human heart and skeletal muscle. Nat Genet. 1996; 13(1):63-9. DOI: 10.1038/ng0596-63. View