title: The dynamic conformational cycle of the group I chaperonin C-termini revealed via molecular dynamics simulation.
abstract: Chaperonins are large ring shaped oligomers that facilitate protein folding by encapsulation within a central cavity. All chaperonins possess flexible C-termini which protrude from the equatorial domain of each subunit into the central cavity. Biochemical evidence suggests that the termini play an important role in the allosteric regulation of the ATPase cycle, in substrate folding and in complex assembly and stability. Despite the tremendous wealth of structural data available for numerous orthologous chaperonins, little structural information is available regarding the residues within the C-terminus. Herein, molecular dynamics simulations are presented which localize the termini throughout the nucleotide cycle of the group I chaperonin, GroE, from Escherichia coli. The simulation results predict that the termini undergo a heretofore unappreciated conformational cycle which is coupled to the nucleotide state of the enzyme. As such, these results have profound implications for the mechanism by which GroE utilizes nucleotide and folds client proteins.
authors.affiliation: Biophysics Program, Stanford University, Stanford, California, United States of America.
authors.forename: Kevin M
authors.initials: KM
authors.lastname: Dalton
authors.affiliation: Department of Biology, Stanford University, Stanford, California, United States of America.
authors.forename: Judith
authors.initials: J
authors.lastname: Frydman
authors.affiliation: Department of Chemistry, Stanford University, Stanford, California, United States of America.
authors.forename: Vijay S
authors.initials: VS
authors.lastname: Pande
mesh_terms: D056384:Group I Chaperonins / Q000737:chemistry* / Q000378:metabolism; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D011485:Protein Binding; D011487:Protein Conformation; D054730:Protein Interaction Domains and Motifs
chemical_list: D056384:Group I Chaperonins
references.citation: Proteins. 2010 Jun;78(8):1950-8
references.pmid: 20408171
references.citation: Cell. 2001 Dec 28;107(7):869-79
references.pmid: 11779463
references.citation: Acta Crystallogr D Biol Crystallogr. 2010 Apr;66(Pt 4):486-501
references.pmid: 20383002
references.citation: EMBO J. 2012 Feb 1;31(3):720-30
references.pmid: 22045336
references.citation: Nature. 2011 Jul 21;475(7356):324-32
references.pmid: 21776078
references.citation: Phys Biol. 2009;6(1):015003
references.pmid: 19208937
references.citation: Nature. 1999 Nov 11;402(6758):147-54
references.pmid: 10647006
references.citation: J Biol Chem. 2008 Mar 14;283(11):6886-96
references.pmid: 18184659
references.citation: Nature. 1994 Oct 13;371(6498):614-9
references.pmid: 7935796
references.citation: Cell. 2012 Mar 30;149(1):113-23
references.pmid: 22445172
references.citation: Proc Natl Acad Sci U S A. 2007 Mar 27;104(13):5342-7
references.pmid: 17372195
references.citation: J Chem Phys. 2013 Apr 28;138(16):165101
references.pmid: 23635172
references.citation: J Biol Chem. 2010 Sep 3;285(36):27958-66
references.pmid: 20573955
references.citation: Nature. 1997 Aug 21;388(6644):741-50
references.pmid: 9285585
references.citation: J Mol Biol. 2003 Apr 4;327(4):843-55
references.pmid: 12654267
references.citation: Arch Biochem Biophys. 2011 Aug 1;512(1):111-8
references.pmid: 21600187
references.citation: Mol Cell. 2007 May 11;26(3):415-26
references.pmid: 17499047
references.citation: J Am Chem Soc. 2012 Aug 1;134(30):12565-77
references.pmid: 22747188
references.citation: Biochemistry. 2001 Sep 25;40(38):11289-93
references.pmid: 11560476
references.citation: Nature. 2010 Jan 21;463(7279):379-83
references.pmid: 20090755
references.citation: J Am Chem Soc. 2008 Sep 10;130(36):11838-9
references.pmid: 18710231
references.citation: FEBS Lett. 2011 Jun 23;585(12):1969-72
references.pmid: 21609718
references.citation: Structure. 2012 May 9;20(5):814-25
references.pmid: 22503819
references.citation: Proc Natl Acad Sci U S A. 2010 Jun 29;107(26):11793-8
references.pmid: 20547872
references.citation: J Bacteriol. 1994 Nov;176(22):6980-5
references.pmid: 7961461
references.citation: Cell. 2011 Jan 21;144(2):240-52
references.pmid: 21241893
references.citation: Annu Rev Cell Dev Biol. 2007;23:115-45
references.pmid: 17489689
references.citation: J Biol Chem. 2014 Aug 15;289(33):23219-32
references.pmid: 24970895
references.citation: Proc Natl Acad Sci U S A. 2007 Jun 19;104(25):10430-4
references.pmid: 17563390
references.citation: J Mol Graph. 1996 Feb;14(1):33-8, 27-8
references.pmid: 8744570
references.citation: Mol Syst Biol. 2009;5:275
references.pmid: 19536198
references.citation: J Am Chem Soc. 2010 Feb 10;132(5):1526-8
references.pmid: 20070076
references.citation: PLoS Genet. 2013;9(2):e1003306
references.pmid: 23437010
references.citation: Cell. 2006 Jun 2;125(5):903-14
references.pmid: 16751100
references.citation: Cell. 2013 Jun 6;153(6):1354-65
references.pmid: 23746846
references.citation: Nature. 1994 Oct 13;371(6498):578-86
references.pmid: 7935790
references.citation: Cell. 1998 Apr 3;93(1):125-38
references.pmid: 9546398
references.citation: EMBO J. 2011 Aug 3;30(15):3078-90
references.pmid: 21701561
references.citation: J Mol Biol. 2004 Jan 30;335(5):1265-78
references.pmid: 14729342
references.citation: Cell. 2001 Oct 19;107(2):223-33
references.pmid: 11672529
references.citation: Cell. 2005 Jul 29;122(2):209-20
references.pmid: 16051146
references.citation: J Chem Theory Comput. 2008 Mar;4(3):435-47
references.pmid: 26620784