title: The ensemble nature of allostery.
abstract: Allostery is the process by which biological macromolecules (mostly proteins) transmit the effect of binding at one site to another, often distal, functional site, allowing for regulation of activity. Recent experimental observations demonstrating that allostery can be facilitated by dynamic and intrinsically disordered proteins have resulted in a new paradigm for understanding allosteric mechanisms, which focuses on the conformational ensemble and the statistical nature of the interactions responsible for the transmission of information. Analysis of allosteric ensembles reveals a rich spectrum of regulatory strategies, as well as a framework to unify the description of allosteric mechanisms from different systems.
authors.affiliation: Department of Biology and T.C. Jenkins Department of Biophysics, Johns Hopkins University, Baltimore, Maryland 21218, USA.
authors.forename: Hesam N
authors.initials: HN
authors.lastname: Motlagh
authors.affiliation: Department of Biology and T.C. Jenkins Department of Biophysics, Johns Hopkins University, Baltimore, Maryland 21218, USA.
authors.forename: James O
authors.initials: JO
authors.lastname: Wrabl
authors.affiliation: Department of Biology and T.C. Jenkins Department of Biophysics, Johns Hopkins University, Baltimore, Maryland 21218, USA.
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Biology and T.C. Jenkins Department of Biophysics, Johns Hopkins University, Baltimore, Maryland 21218, USA.
authors.forename: Vincent J
authors.initials: VJ
authors.lastname: Hilser
mesh_terms: D000494:Allosteric Regulation; D000495:Allosteric Site; D006454:Hemoglobins / Q000737:chemistry / Q000378:metabolism; D008024:Ligands; D008958:Models, Molecular; D058767:Protein Unfolding; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism*; D013816:Thermodynamics
chemical_list: D006454:Hemoglobins; D008024:Ligands; D011506:Proteins
references.citation: J Phys Chem B. 2010 Dec 16;114(49):16105-11
references.pmid: 20863145
references.citation: Proc Natl Acad Sci U S A. 2009 Oct 27;106(43):18249-54
references.pmid: 19828436
references.citation: Annu Rev Biophys Biomol Struct. 2004;33:53-73
references.pmid: 15139804
references.citation: Methods Enzymol. 2001;339:204-38
references.pmid: 11462813
references.citation: J Mol Recognit. 2005 Sep-Oct;18(5):343-84
references.pmid: 16094605
references.citation: Pac Symp Biocomput. 2012;:94-103
references.pmid: 22174266
references.citation: Nature. 2013 Nov 14;503(7475):295-9
references.pmid: 24121438
references.citation: Proc Natl Acad Sci U S A. 2007 Jun 5;104(23):9615-20
references.pmid: 17535901
references.citation: Proc Natl Acad Sci U S A. 2000 Oct 24;97(22):12020-5
references.pmid: 11035796
references.citation: Annu Rev Biophys. 2013;42:169-89
references.pmid: 23451894
references.citation: J Cell Comp Physiol. 1959 Dec;54:245-58
references.pmid: 14411189
references.citation: Chem Rev. 2006 May;106(5):1672-99
references.pmid: 16683749
references.citation: Proc Natl Acad Sci U S A. 2007 May 15;104(20):8311-5
references.pmid: 17494761
references.citation: Curr Opin Struct Biol. 2003 Dec;13(6):748-57
references.pmid: 14675554
references.citation: Proc Natl Acad Sci U S A. 2003 Jan 21;100(2):517-20
references.pmid: 12525687
references.citation: Annu Rev Biophys. 2012;41:429-52
references.pmid: 22577825
references.citation: Nature. 1960 Feb 13;185(4711):416-22
references.pmid: 18990801
references.citation: Science. 2009 Apr 10;324(5924):198-203
references.pmid: 19359576
references.citation: Nat Struct Biol. 1997 Jan;4(1):10-9
references.pmid: 8989315
references.citation: Nature. 2013 Jun 20;498(7454):390-4
references.pmid: 23783631
references.citation: Nat Struct Mol Biol. 2006 Sep;13(9):831-8
references.pmid: 16906160
references.citation: Chemistry. 2012 Jun 25;18(26):7984-99
references.pmid: 22688954
references.citation: Proteins. 2004 Nov 15;57(3):433-43
references.pmid: 15382234
references.citation: Proteins. 2002 Nov 1;49(2):181-90
references.pmid: 12210999
references.citation: Structure. 2011 Nov 9;19(11):1582-90
references.pmid: 22078558
references.citation: Curr Opin Struct Biol. 2007 Feb;17(1):3-14
references.pmid: 17250999
references.citation: J Biol Chem. 1992 Aug 25;267(24):17248-56
references.pmid: 1512262
references.citation: J Mol Biol. 2008 Aug 1;381(1):89-101
references.pmid: 18586268
references.citation: Proc Natl Acad Sci U S A. 2009 Oct 6;106(40):16984-9
references.pmid: 19805185
references.citation: Nat Struct Mol Biol. 2011 Mar;18(3):288-94
references.pmid: 21278754
references.citation: Structure. 2011 Jul 13;19(7):967-75
references.pmid: 21742263
references.citation: Annu Rev Biophys. 2012;41:103-33
references.pmid: 22224598
references.citation: J Mol Biol. 2013 Feb 8;425(3):647-61
references.pmid: 23228330
references.citation: Annu Rev Biophys. 2012;41:585-609
references.pmid: 22577828
references.citation: Nat Struct Biol. 2000 Jan;7(1):72-7
references.pmid: 10625431
references.citation: Biochemistry. 2005 Sep 27;44(38):12627-39
references.pmid: 16171378
references.citation: Biophys J. 2013 Aug 20;105(4):1027-36
references.pmid: 23972854
references.citation: Science. 1992 May 1;256(5057):655-9
references.pmid: 1585178
references.citation: Annu Rev Biophys Biomol Struct. 2002;31:235-56
references.pmid: 11988469
references.citation: Curr Opin Struct Biol. 2011 Jun;21(3):426-31
references.pmid: 21530234
references.citation: Protein Sci. 2008 Aug;17(8):1295-307
references.pmid: 18560010
references.citation: Nature. 2009 Dec 3;462(7273):669-73
references.pmid: 19956261
references.citation: Proteins. 2013 Jul;81(7):1097-101
references.pmid: 23508936
references.citation: Top Curr Chem. 2013;328:99-153
references.pmid: 22576356
references.citation: Elife. 2012 Dec 18;1:e00311
references.pmid: 23251785
references.citation: Annu Rev Phys Chem. 1997;48:545-600
references.pmid: 9348663
references.citation: Nature. 2009 Nov 19;462(7271):368-72
references.pmid: 19924217
references.citation: J Mol Biol. 1999 Oct 22;293(2):321-31
references.pmid: 10550212
references.citation: Biochemistry. 2004 Apr 6;43(13):3844-52
references.pmid: 15049691
references.citation: J Phys Chem B. 2013 Mar 21;117(11):3063-73
references.pmid: 23445323
references.citation: Proc Natl Acad Sci U S A. 1982 Feb;79(4):1129-33
references.pmid: 6461856
references.citation: Protein Sci. 2013 Apr;22(4):475-85
references.pmid: 23400970
references.citation: Cold Spring Harb Symp Quant Biol. 1961;26:313-8
references.pmid: 13878122
references.citation: Chem Rev. 2006 May;106(5):1624-71
references.pmid: 16683748
references.citation: Biochemistry. 2006 Jun 6;45(22):6873-88
references.pmid: 16734424
references.citation: Structure. 2013 Sep 3;21(9):1492-9
references.pmid: 24010708
references.citation: Protein Sci. 1996 Dec;5(12):2647-50
references.pmid: 8976574
references.citation: Annu Rev Biochem. 1972;41:815-42
references.pmid: 4117310
references.citation: Int J Biochem Cell Biol. 2011 Aug;43(8):1090-103
references.pmid: 21501695
references.citation: J Mol Biol. 1963 Apr;6:306-29
references.pmid: 13936070
references.citation: J Mol Biol. 2007 Nov 9;373(5):1361-73
references.pmid: 17900617
references.citation: J Mol Biol. 1996 Oct 25;263(2):369-82
references.pmid: 8913313
references.citation: Science. 1991 Dec 13;254(5038):1598-603
references.pmid: 1749933
references.citation: Nature. 2007 Jul 19;448(7151):325-9
references.pmid: 17637663
references.citation: Trends Biochem Sci. 2008 Sep;33(9):420-5
references.pmid: 18706817
references.citation: Science. 2013 Feb 22;339(6122):913-5
references.pmid: 23430643
references.citation: PLoS Biol. 2013 Sep;11(9):e1001651
references.pmid: 24058293
references.citation: Proc Natl Acad Sci U S A. 2009 Dec 29;106(52):22263-8
references.pmid: 20080791
references.citation: Mol Biosyst. 2008 Nov;4(11):1058-69
references.pmid: 18931781
references.citation: Mol Cell. 2007 Apr 13;26(1):27-39
references.pmid: 17434124
references.citation: Curr Opin Struct Biol. 2011 Apr;21(2):167-72
references.pmid: 21333527
references.citation: Science. 1999 Oct 8;286(5438):295-9
references.pmid: 10514373
references.citation: Annu Rev Biophys Biomol Struct. 1998;27:1-34
references.pmid: 9646860
references.citation: Nat Chem Biol. 2010 May;6(5):352-8
references.pmid: 20383153
references.citation: Biochemistry. 1966 Jan;5(1):365-85
references.pmid: 5938952
references.citation: FEBS Lett. 2009 Jun 5;583(11):1692-8
references.pmid: 19303011
references.citation: Nat Struct Biol. 2003 Jan;10(1):59-69
references.pmid: 12483203
references.citation: Nat Struct Biol. 1999 Apr;6(4):351-8
references.pmid: 10201404
references.citation: Eur Biophys J. 1984;11(2):103-9
references.pmid: 6544679
references.citation: Proc Natl Acad Sci U S A. 2006 May 30;103(22):8390-5
references.pmid: 16717195
references.citation: Curr Opin Struct Biol. 2013 Feb;23(1):75-81
references.pmid: 23246280
references.citation: Proc Natl Acad Sci U S A. 2012 Mar 13;109(11):4134-9
references.pmid: 22388747
references.citation: Science. 2010 Feb 5;327(5966):685-9
references.pmid: 20133571
references.citation: Nucleic Acids Res. 2008 Jan;36(Database issue):D419-25
references.pmid: 18000004
references.citation: Mol Biosyst. 2009 Mar;5(3):207-16
references.pmid: 19225609
references.citation: Nature. 1970 Nov 21;228(5273):726-39
references.pmid: 5528785
references.citation: Curr Opin Struct Biol. 2011 Feb;21(1):62-7
references.pmid: 21109422
references.citation: Nature. 2012 Aug 9;488(7410):236-40
references.pmid: 22801505
references.citation: Curr Protein Pept Sci. 2009 Apr;10(2):116-27
references.pmid: 19355979
references.citation: Proc Natl Acad Sci U S A. 2005 Nov 22;102(47):17002-7
references.pmid: 16284250
references.citation: Science. 2005 Jun 3;308(5727):1424-8
references.pmid: 15933191
references.citation: J Chem Theory Comput. 2012 Aug 14;8(8):2949-2961
references.pmid: 23139645
references.citation: J Am Chem Soc. 2011 May 11;133(18):7152-8
references.pmid: 21491910
references.citation: PLoS Comput Biol. 2009 Feb;5(2):e1000293
references.pmid: 19229311
references.citation: PLoS Comput Biol. 2011 Sep;7(9):e1002201
references.pmid: 21980279
references.citation: Nature. 2008 Oct 2;455(7213):693-6
references.pmid: 18833280
references.citation: IUBMB Life. 2007 Aug-Sep;59(8-9):586-99
references.pmid: 17701554
references.citation: J Mol Biol. 1965 May;12:88-118
references.pmid: 14343300
references.citation: Structure. 2009 Sep 9;17(9):1169-85
references.pmid: 19748338
references.citation: Nature. 2005 Jan 13;433(7022):128-32
references.pmid: 15650731
references.citation: Proc Natl Acad Sci U S A. 2013 Aug 6;110(32):12867-74
references.pmid: 23868852
references.citation: Curr Opin Struct Biol. 2011 Jun;21(3):419-25
references.pmid: 21514142
references.citation: Cold Spring Harb Symp Quant Biol. 1961;26:389-401
references.pmid: 14475415
references.citation: Cell. 2010 Jan 22;140(2):246-56
references.pmid: 20141838
references.citation: Cell. 2010 Jul 9;142(1):101-11
references.pmid: 20603017
references.citation: Proc Natl Acad Sci U S A. 2011 Sep 27;108(39):16247-52
references.pmid: 21918110