Conformational changes linked to ADP release from human cardiac myosin bound to actin-tropomyosin.
Journal
The Journal of general physiology
ISSN: 1540-7748
Titre abrégé: J Gen Physiol
Pays: United States
ID NLM: 2985110R
Informations de publication
Date de publication:
06 03 2023
06 03 2023
Historique:
received:
23
09
2022
revised:
11
11
2022
accepted:
14
12
2022
entrez:
12
1
2023
pubmed:
13
1
2023
medline:
17
1
2023
Statut:
ppublish
Résumé
Following binding to the thin filament, β-cardiac myosin couples ATP-hydrolysis to conformational rearrangements in the myosin motor that drive myofilament sliding and cardiac ventricular contraction. However, key features of the cardiac-specific actin-myosin interaction remain uncertain, including the structural effect of ADP release from myosin, which is rate-limiting during force generation. In fact, ADP release slows under experimental load or in the intact heart due to the afterload, thereby adjusting cardiac muscle power output to meet physiological demands. To further elucidate the structural basis of this fundamental process, we used a combination of cryo-EM reconstruction methodologies to determine structures of the human cardiac actin-myosin-tropomyosin filament complex at better than 3.4 Å-resolution in the presence and in the absence of Mg2+·ADP. Focused refinements of the myosin motor head and its essential light chains in these reconstructions reveal that small changes in the nucleotide-binding site are coupled to significant rigid body movements of the myosin converter domain and a 16-degree lever arm swing. Our structures provide a mechanistic framework to understand the effect of ADP binding and release on human cardiac β-myosin, and offer insights into the force-sensing mechanism displayed by the cardiac myosin motor.
Identifiants
pubmed: 36633586
pii: 213802
doi: 10.1085/jgp.202213267
pmc: PMC9859928
pii:
doi:
Substances chimiques
Actins
0
Tropomyosin
0
Cardiac Myosins
EC 3.6.1.-
Myosins
EC 3.6.4.1
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NHLBI NIH HHS
ID : R01 HL036153
Pays : United States
Organisme : NIGMS NIH HHS
ID : U24 GM129541
Pays : United States
Organisme : NCRR NIH HHS
ID : S10 RR025434
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL127699
Pays : United States
Organisme : NIH HHS
ID : R01HL036153
Pays : United States
Organisme : NHLBI NIH HHS
ID : T32 HL007969
Pays : United States
Informations de copyright
© 2023 Doran et al.
Références
Elife. 2019 Sep 17;8:
pubmed: 31526481
J Struct Biol. 2015 Nov;192(2):216-21
pubmed: 26278980
J Mol Biol. 2016 Jul 3;428(13):2709-29
pubmed: 27139643
Nature. 2016 Jun 30;534(7609):724-8
pubmed: 27324845
Biophys J. 2020 Aug 18;119(4):821-830
pubmed: 32730789
Biophys J. 2014 Dec 16;107(12):L41-L44
pubmed: 25517169
Dev Cell. 2015 May 26;33(4):401-12
pubmed: 25936506
Nature. 1990 Nov 15;348(6298):217-21
pubmed: 2234090
Nat Commun. 2018 Sep 21;9(1):3838
pubmed: 30242219
Biophys J. 2016 Jun 21;110(12):2568-2576
pubmed: 27332116
Elife. 2021 Nov 23;10:
pubmed: 34812732
Biochemistry. 1971 Dec 7;10(25):4617-24
pubmed: 4258719
Proc Natl Acad Sci U S A. 2015 Jun 30;112(26):E3337-44
pubmed: 26056287
Proc Natl Acad Sci U S A. 2006 Apr 18;103(16):6136-41
pubmed: 16603626
Elife. 2020 Sep 24;9:
pubmed: 32969337
J Biol Chem. 2002 Jul 5;277(27):24114-9
pubmed: 11959853
Cytoskeleton (Hoboken). 2021 Sep;78(9):448-458
pubmed: 35278035
EMBO J. 1982;1(8):945-51
pubmed: 6329717
Biochim Biophys Acta. 2012 Jan;1823(1):2-14
pubmed: 21839118
Proc Natl Acad Sci U S A. 2021 Aug 3;118(31):
pubmed: 34326268
Nat Commun. 2018 Oct 1;9(1):4019
pubmed: 30275503
Biophys J. 2021 Jun 1;120(11):2222-2236
pubmed: 33864791
Biophys J. 1995 Apr;68(4 Suppl):194S-199S; discussion 199S-201S
pubmed: 7787067
Cardiovasc Res. 2008 Mar 1;77(4):659-66
pubmed: 18056765
J Biol Chem. 2006 Nov 24;281(47):36102-9
pubmed: 16982629
Proc Natl Acad Sci U S A. 2016 Jun 14;113(24):6701-6
pubmed: 27247418
Nat Commun. 2020 Jan 9;11(1):153
pubmed: 31919429
J Biol Chem. 2019 Nov 15;294(46):17314-17325
pubmed: 31578282
Sci Adv. 2022 Jul 22;8(29):eabl4733
pubmed: 35857845
Nature. 1995 Dec 14;378(6558):748-51
pubmed: 7501026
Adv Protein Chem. 2005;71:161-93
pubmed: 16230112
Nature. 2021 Aug;596(7873):583-589
pubmed: 34265844
Adv Exp Med Biol. 2020;1239:245-316
pubmed: 32451863
Science. 1969 Jun 20;164(3886):1356-65
pubmed: 4181952
Protein Sci. 2021 Jan;30(1):70-82
pubmed: 32881101
Philos Trans R Soc Lond B Biol Sci. 2004 Dec 29;359(1452):1867-77
pubmed: 15647162
Nucleic Acids Res. 2003 Jul 1;31(13):3381-5
pubmed: 12824332
Elife. 2021 Feb 19;10:
pubmed: 33605878
Biopolymers. 2016 Aug;105(8):483-91
pubmed: 27061920
EMBO J. 2004 Nov 24;23(23):4527-37
pubmed: 15510214
Trends Biochem Sci. 2016 Dec;41(12):989-997
pubmed: 27717739
J Biol Chem. 2014 Aug 22;289(34):23977-91
pubmed: 25006251
Nat Commun. 2022 Aug 5;13(1):4575
pubmed: 35931685
Biochemistry. 2015 Mar 17;54(10):1963-75
pubmed: 25680381
Structure. 2021 Jan 7;29(1):50-60.e4
pubmed: 33065066
Nat Struct Biol. 2000 Dec;7(12):1147-55
pubmed: 11101898
J Mol Biol. 1997 Feb 14;266(1):8-14
pubmed: 9054965
J Biol Chem. 1984 Apr 25;259(8):5045-53
pubmed: 6715335
Biochemistry. 1998 Feb 17;37(7):1969-78
pubmed: 9485324
Nat Commun. 2015 Aug 04;6:7931
pubmed: 26239258
J Biol Chem. 2017 Mar 3;292(9):3768-3778
pubmed: 28082673
J Struct Biol. 2005 Jul;151(1):41-60
pubmed: 15890530
Proc Natl Acad Sci U S A. 2018 Feb 6;115(6):1292-1297
pubmed: 29358376
Nat Methods. 2017 Apr;14(4):331-332
pubmed: 28250466
J Biol Chem. 2019 Feb 1;294(5):1554-1567
pubmed: 30518549
Biophys J. 2020 Jan 21;118(2):303-312
pubmed: 31882250
Biophys J. 2022 Jun 21;121(12):2449-2460
pubmed: 35591788
J Biol Chem. 2005 Feb 18;280(7):6072-9
pubmed: 15579901
Biochemistry. 2000 Sep 26;39(38):11602-8
pubmed: 10995227
Elife. 2017 Dec 04;6:
pubmed: 29199952
Biology (Basel). 2021 Nov 23;10(12):
pubmed: 34943138
J Biol Chem. 2001 Feb 2;276(5):2998-3003
pubmed: 11042210