title: Protein sectors: evolutionary units of three-dimensional structure.
abstract: Proteins display a hierarchy of structural features at primary, secondary, tertiary, and higher-order levels, an organization that guides our current understanding of their biological properties and evolutionary origins. Here, we reveal a structural organization distinct from this traditional hierarchy by statistical analysis of correlated evolution between amino acids. Applied to the S1A serine proteases, the analysis indicates a decomposition of the protein into three quasi-independent groups of correlated amino acids that we term "protein sectors." Each sector is physically connected in the tertiary structure, has a distinct functional role, and constitutes an independent mode of sequence divergence in the protein family. Functionally relevant sectors are evident in other protein families as well, suggesting that they may be general features of proteins. We propose that sectors represent a structural organization of proteins that reflects their evolutionary histories.
authors.affiliation: Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, TX 75390-9050, USA.
authors.forename: Najeeb
authors.initials: N
authors.lastname: Halabi
authors.forename: Olivier
authors.initials: O
authors.lastname: Rivoire
authors.forename: Stanislas
authors.initials: S
authors.lastname: Leibler
authors.forename: Rama
authors.initials: R
authors.lastname: Ranganathan
mesh_terms: D000595:Amino Acid Sequence; D000596:Amino Acids / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D000818:Animals; D017124:Conserved Sequence; D004795:Enzyme Stability; D019143:Evolution, Molecular; D006801:Humans; D008958:Models, Molecular; D051381:Rats; D012697:Serine Endopeptidases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism
chemical_list: D000596:Amino Acids; D012697:Serine Endopeptidases
references.citation: Science. 2009 Apr 10;324(5924):198-203
references.pmid: 19359576
references.citation: Cell. 2008 Jun 13;133(6):1043-54
references.pmid: 18555780
references.citation: J Mol Biol. 1996 Mar 29;257(2):342-58
references.pmid: 8609628
references.citation: Science. 2003 Aug 29;301(5637):1196-202
references.pmid: 12947189
references.citation: J Biochem. 2004 Jan;135(1):93-9
references.pmid: 14999014
references.citation: Nucleic Acids Res. 1997 Dec 15;25(24):4876-82
references.pmid: 9396791
references.citation: J Mol Biol. 2004 Jan 23;335(4):1105-15
references.pmid: 14698303
references.citation: Proc Natl Acad Sci U S A. 2003 Nov 25;100(24):14445-50
references.pmid: 14623969
references.citation: J Mol Biol. 2000 Oct 27;303(3):433-46
references.pmid: 11031119
references.citation: Nature. 2005 Sep 22;437(7058):512-8
references.pmid: 16177782
references.citation: Protein Eng. 1997 Apr;10(4):405-11
references.pmid: 9194165
references.citation: Biochemistry. 1994 Jul 26;33(29):8757-63
references.pmid: 8038165
references.citation: Annu Rev Biochem. 2005;74:867-900
references.pmid: 15954844
references.citation: Chem Rev. 2002 Dec;102(12):4501-24
references.pmid: 12475199
references.citation: Proteins. 2002 Sep 1;48(4):611-7
references.pmid: 12211028
references.citation: J Biol Chem. 2004 Jul 16;279(29):30751-9
references.pmid: 15123647
references.citation: J Biol Chem. 2004 Apr 30;279(18):19046-50
references.pmid: 15023994
references.citation: Cell. 2004 Feb 6;116(3):417-29
references.pmid: 15016376
references.citation: Mol Biol Evol. 2005 Jul;22(7):1627-34
references.pmid: 15858204
references.citation: Proc Natl Acad Sci U S A. 2007 Jan 9;104(2):513-8
references.pmid: 17197416
references.citation: Biochemistry. 1995 Feb 7;34(5):1489-99
references.pmid: 7849008
references.citation: Cell. 1994 Mar 11;76(5):933-45
references.pmid: 7510218
references.citation: J Mol Biol. 2005 Aug 12;351(2):345-54
references.pmid: 16005893
references.citation: Trends Biochem Sci. 2000 Jun;25(6):300-2
references.pmid: 10838572
references.citation: Proc Natl Acad Sci U S A. 1999 Mar 2;96(5):1852-7
references.pmid: 10051558
references.citation: Fold Des. 1997;2(3):S25-32
references.pmid: 9218963
references.citation: Nucleic Acids Res. 2008 Jan;36(Database issue):D320-5
references.pmid: 17991683
references.citation: Protein Sci. 1999 Jan;8(1):253-8
references.pmid: 10210204
references.citation: Sci STKE. 2003 Apr 22;2003(179):RE8
references.pmid: 12709533
references.citation: Biochemistry. 1992 Mar 31;31(12):3059-64
references.pmid: 1554694
references.citation: Science. 2008 Oct 17;322(5900):438-42
references.pmid: 18927392
references.citation: Braz J Med Biol Res. 2003 Dec;36(12):1621-7
references.pmid: 14666246
references.citation: Nat Struct Biol. 2003 Jul;10(7):527-34
references.pmid: 12819769
references.citation: Nat Struct Biol. 1999 Nov;6(11):1016-24
references.pmid: 10542092
references.citation: Proc Natl Acad Sci U S A. 2007 Dec 11;104(50):19813-8
references.pmid: 18077413
references.citation: Proc Natl Acad Sci U S A. 2002 Mar 5;99(5):2794-9
references.pmid: 11867722
references.citation: Protein Eng. 1996 Nov;9(11):941-8
references.pmid: 8961347
references.citation: PLoS Biol. 2009 Mar 3;7(3):e47
references.pmid: 19260762
references.citation: Nat Struct Biol. 1999 Nov;6(11):1010-6
references.pmid: 10542091
references.citation: Protein Sci. 2006 Jun;15(6):1229-38
references.pmid: 16672242
references.citation: Cell. 1996 Jun 28;85(7):1067-76
references.pmid: 8674113
references.citation: Science. 2003 Sep 12;301(5639):1541-4
references.pmid: 12970567
references.citation: Biol Chem. 1996 Jul-Aug;377(7-8):465-70
references.pmid: 8922280
references.citation: Methods Enzymol. 1994;244:19-61
references.pmid: 7845208
references.citation: Nature. 2005 Sep 22;437(7058):579-83
references.pmid: 16177795
references.citation: Cell. 2007 Oct 5;131(1):80-92
references.pmid: 17923089
references.citation: Science. 1996 Aug 2;273(5275):595-603
references.pmid: 8662544
references.citation: Proc Natl Acad Sci U S A. 1994 Jan 4;91(1):98-102
references.pmid: 8278414
references.citation: Science. 1985 Apr 19;228(4697):291-7
references.pmid: 3838593
references.citation: Annu Rev Genomics Hum Genet. 2006;7:61-80
references.pmid: 16824020
references.citation: Science. 1999 Oct 8;286(5438):295-9
references.pmid: 10514373
references.citation: Annu Rev Biophys Biomol Struct. 1997;26:259-88
references.pmid: 9241420
references.citation: Nat Struct Biol. 2003 Jan;10(1):59-69
references.pmid: 12483203
references.citation: J Mol Biol. 1982 Sep 15;160(2):309-23
references.pmid: 6816943
references.citation: Cell. 2008 Sep 5;134(5):793-803
references.pmid: 18775312
references.citation: Biochemistry. 2007 Dec 11;46(49):14001-9
references.pmid: 18001137
references.citation: J Mol Biol. 1982 Sep 15;160(2):325-42
references.pmid: 7175935
references.citation: Eur J Biochem. 2001 Dec;268(23):6238-46
references.pmid: 11733020
references.citation: Genomics. 2004 Jul;84(1):147-56
references.pmid: 15203212
references.citation: Nucleic Acids Res. 1997 Sep 1;25(17):3389-402
references.pmid: 9254694
references.citation: Proteins. 2004 Sep 1;56(4):679-84
references.pmid: 15281121
references.citation: J Mol Biol. 1987 Jun 20;195(4):957-61
references.pmid: 3656439
references.citation: Science. 2002 Feb 22;295(5559):1520-3
references.pmid: 11859194
references.citation: J Mol Biol. 1999 Oct 22;293(2):333-42
references.pmid: 10529349
references.citation: J Mol Biol. 2008 Sep 19;381(5):1157-67
references.pmid: 18590738
references.citation: Proteins. 1999;Suppl 3:177-85
references.pmid: 10526366
references.citation: Science. 1993 Jul 30;261(5121):620-2
references.pmid: 8342029
references.citation: Structure. 2003 Apr;11(4):469-79
references.pmid: 12679024
references.citation: Protein Eng. 1994 Mar;7(3):349-58
references.pmid: 8177884
references.citation: Biochim Biophys Acta. 2000 Mar 7;1477(1-2):307-23
references.pmid: 10708866
references.citation: Science. 1995 Jan 20;267(5196):383-6
references.pmid: 7529940
references.citation: Phys Rev E Stat Nonlin Soft Matter Phys. 2002 Jun;65(6 Pt 2):066126
references.pmid: 12188802
references.citation: Mol Biol Evol. 2000 Jan;17(1):164-78
references.pmid: 10666716
references.citation: J Biol Chem. 2007 Sep 14;282(37):27165-27170
references.pmid: 17636263
references.citation: Arch Biochem Biophys. 2000 Oct 1;382(1):57-62
references.pmid: 11051097
references.citation: Bioinformatics. 2007 Aug 1;23(15):1875-82
references.pmid: 17519246
references.citation: Science. 1990 Mar 16;247(4948):1306-10
references.pmid: 2315699
references.citation: Proteins. 1994 Apr;18(4):309-17
references.pmid: 8208723
references.citation: Protein Sci. 2000 Jul;9(7):1416-9
references.pmid: 10933511
references.citation: Mol Cell. 2004 Mar 12;13(5):665-76
references.pmid: 15023337
references.citation: Biochemistry. 2008 Jul 1;47(26):6752-61
references.pmid: 18540681