title: Pi release from myosin: a simulation analysis of possible pathways.
abstract: The release of phosphate (Pi) is an important element in actomyosin function and has been shown to be accelerated by the binding of myosin to actin. To provide information about the structural elements important for Pi release, possible escape pathways from various isolated myosin II structures have been determined by molecular dynamics simulations designed for studying such slow processes. The residues forming the pathways were identified and their role was evaluated by mutant simulations. Pi release is slow in the pre-powerstroke structure, an important element in preventing the powerstroke prior to actin binding, and is much more rapid for Pi modeled into the post-rigor and rigor-like structures. The previously proposed backdoor route is dominant in the pre-powerstroke and post-rigor states, whereas a different path is most important in the rigor-like state. This finding suggests a mechanism for the actin-activated acceleration of Pi release.
authors.affiliation: Laboratoire de Chimie Biophysique, ISIS, Université de Strasbourg, 67000 Strasbourg, France. mcecchini@isis.u-strasbg.fr
authors.forename: Marco
authors.initials: M
authors.lastname: Cecchini
authors.forename: Yuri
authors.initials: Y
authors.lastname: Alexeev
authors.forename: Martin
authors.initials: M
authors.lastname: Karplus
mesh_terms: D000199:Actins / Q000737:chemistry; D000818:Animals; D003198:Computer Simulation; D018360:Crystallography, X-Ray / Q000379:methods; D004252:DNA Mutational Analysis; D004023:Dictyostelium / Q000378:metabolism; D007700:Kinetics; D008958:Models, Molecular; D008968:Molecular Conformation; D009218:Myosins / Q000737:chemistry*; D010710:Phosphates / Q000737:chemistry; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D013696:Temperature
chemical_list: D000199:Actins; D010710:Phosphates; D009218:Myosins
references.citation: Biochemistry. 1996 Apr 30;35(17):5404-17
references.pmid: 8611530
references.citation: Biochemistry. 1971 Dec 7;10(25):4617-24
references.pmid: 4258719
references.citation: Biochemistry. 1997 Sep 30;36(39):11828-36
references.pmid: 9305974
references.citation: Science. 1993 Jul 2;261(5117):50-8
references.pmid: 8316857
references.citation: Nat Struct Biol. 2003 Oct;10(10):826-30
references.pmid: 14502270
references.citation: J Biol Chem. 2004 Sep 17;279(38):40100-11
references.pmid: 15254035
references.citation: Philos Trans R Soc Lond B Biol Sci. 2004 Dec 29;359(1452):1829-41
references.pmid: 15647159
references.citation: Proc Natl Acad Sci U S A. 2002 Oct 1;99(20):12562-6
references.pmid: 12271136
references.citation: Biochemistry. 1980 Apr 1;19(7):1276-83
references.pmid: 6892994
references.citation: J Biol Chem. 1992 Nov 5;267(31):22022-34
references.pmid: 1429552
references.citation: Biophys J. 2006 Sep 1;91(5):1844-57
references.pmid: 16751246
references.citation: J Biol Chem. 2008 Mar 28;283(13):8153-63
references.pmid: 18211892
references.citation: PLoS Comput Biol. 2008 Aug 15;4(8):e1000129
references.pmid: 18704171
references.citation: EMBO J. 1982;1(8):945-51
references.pmid: 6329717
references.citation: Philos Trans R Soc Lond B Biol Sci. 2004 Dec 29;359(1452):1819-28
references.pmid: 15647158
references.citation: J Cell Biol. 1996 Oct;135(2):291-302
references.pmid: 8896589
references.citation: Phys Rev A Gen Phys. 1985 Mar;31(3):1695-1697
references.pmid: 9895674
references.citation: Proc Natl Acad Sci U S A. 1998 Jun 9;95(12):6653-8
references.pmid: 9618467
references.citation: Biophys J. 2004 Jun;86(6):3794-803
references.pmid: 15189875
references.citation: Curr Opin Struct Biol. 2004 Apr;14(2):250-9
references.pmid: 15093841
references.citation: Structure. 2007 May;15(5):553-64
references.pmid: 17502101
references.citation: Curr Opin Struct Biol. 2001 Apr;11(2):182-94
references.pmid: 11297926
references.citation: Adv Protein Chem. 2005;71:161-93
references.pmid: 16230112
references.citation: Proc Natl Acad Sci U S A. 1999 Nov 23;96(24):13726-31
references.pmid: 10570140
references.citation: J Comput Chem. 2009 Jul 30;30(10):1545-614
references.pmid: 19444816
references.citation: Biochemistry. 1995 Jul 18;34(28):8960-72
references.pmid: 7619795
references.citation: Nature. 2003 Sep 25;425(6956):419-23
references.pmid: 14508494
references.citation: Biophys J. 1995 Apr;68(4 Suppl):44S-47S; discussion 47S-49S
references.pmid: 7787099
references.citation: J Mol Biol. 2000 Nov 10;303(5):797-811
references.pmid: 11061976
references.citation: Science. 1993 Jul 2;261(5117):58-65
references.pmid: 8316858
references.citation: J Mol Biol. 1999 Aug 6;291(1):101-15
references.pmid: 10438609
references.citation: Structure. 1996 Aug 15;4(8):969-87
references.pmid: 8805581
references.citation: Proc Natl Acad Sci U S A. 2005 May 10;102(19):6873-8
references.pmid: 15863618
references.citation: Science. 1989 Jun 2;244(4908):1081-5
references.pmid: 2471267
references.citation: Proteins. 2008 May 15;71(3):1231-6
references.pmid: 18041761
references.citation: Biophys J. 1996 Apr;70(4):1590-602
references.pmid: 8785318
references.citation: Annu Rev Biochem. 1999;68:687-728
references.pmid: 10872464
references.citation: J Muscle Res Cell Motil. 2002;23(7-8):673-83
references.pmid: 12952066
references.citation: Nature. 2003 Sep 25;425(6956):423-7
references.pmid: 14508495