Prototypes of elementary functional loops unravel evolutionary connections between protein functions.
BACKGROUND
Earlier studies of protein structure revealed closed loops with a characteristic size 25-30 residues and ring-like shape as a basic universal structural element of globular proteins. Elementary functional loops (EFLs) have specific signatures and provide functional residues important for binding/activation and principal chemical transformation steps of the enzymatic reaction. The goal of this work is to show how these functional loops evolved from pre-domain peptides and to find a set of prototypes from which the EFLs of contemporary proteins originated.


RESULTS
This article describes a computational method for deriving prototypes of EFLs based on the sequences of complete genomes. The procedure comprises the iterative derivation of sequence profiles followed by their hierarchical clustering. The scoring function takes into account information content on profile positions, thus preserving the signature. The statistical significance of scores is evaluated from the empirical distribution of scores of the background model. A set of prototypes of EFLs from archaeal proteomes is derived. This set delineates evolutionary connections between major functions and illuminates how folds and functions emerged in pre-domain evolution as a combination of prototypes.
Goncearenco
Alexander
A
Bergen Center for Computational Science and Department of Informatics, University of Bergen, Bergen, Norway.
Berezovsky
Igor N
IN
D020816:Amino Acid Motifs / Q000235:genetics; D000595:Amino Acid Sequence; D019843:Archaeal Proteins / Q000737:chemistry* / Q000235:genetics; D001483:Base Sequence; D019295:Computational Biology / Q000379:methods*; D019143:Evolution, Molecular; D020745:Genome, Archaeal; D008958:Models, Molecular; D008969:Molecular Sequence Data; D017510:Protein Folding; D020543:Proteome
D019843:Archaeal Proteins; D020543:Proteome
Bioinformatics. 2006 Jul 1;22(13):1658-9
16731699
Nucleic Acids Res. 2007 Jan;35(Database issue):D253-9
17068077
Proc Natl Acad Sci U S A. 2008 Apr 8;105(14):5441-6
18385384
EMBO J. 2004 Aug 18;23(16):3196-205
15272305
J Mol Biol. 2002 Aug 30;321(5):741-65
12206759
Protein Eng. 1999 Feb;12(2):85-94
10195279
J Mol Biol. 2001 Apr 13;307(5):1419-26
11292352
Curr Opin Chem Biol. 2006 Oct;10(5):492-7
16935022
Nucleic Acids Res. 2009 Feb;37(3):815-24
19088134
J Biol Chem. 2009 Jun 26;284(26):17796-807
19244233
Nat Genet. 2005 Jan;37(1):73-6
15568024
Protein Sci. 1998 Feb;7(2):233-42
9521098
J Mol Biol. 2001 Nov 2;313(4):903-19
11697912
Nucleic Acids Res. 1997 Sep 1;25(17):3389-402
9254694
Nucleic Acids Res. 2010 Jan;38(Database issue):D161-6
19858104
Trends Biochem Sci. 2005 Nov;30(11):622-9
16214343
Bioinformatics. 2000 Jul;16(7):613-8
11038331
J Struct Biol. 2001 May-Jun;134(2-3):191-203
11551179
Nucleic Acids Res. 2000 Jan 1;28(1):254-6
10592239
Nucleic Acids Res. 2004 Jan 1;32(Database issue):D138-41
14681378
Nature. 1996 Apr 25;380(6576):730-4
8614471
J Mol Biol. 2002 Apr 26;318(2):595-608
12051862
Nature. 1974 Jul 19;250(463):194-9
4368490
Nucleic Acids Res. 2000 Jan 1;28(1):257-9
10592240
Science. 2009 Apr 10;324(5924):203-7
19359577
Bioinformatics. 2009 Aug 1;25(15):1862-8
19470584
Nucleic Acids Res. 2007;35(14):4678-85
17596268
J Mol Biol. 2009 Jul 17;390(3):560-77
19447117
Science. 2003 Jun 13;300(5626):1701-3
12805536
Nucleic Acids Res. 2000 Jan 1;28(1):304-5
10592255
Nucleic Acids Res. 2009 Jan;37(Database issue):D205-10
18984618
Protein Eng. 2003 Mar;16(3):161-7
12702795
FEBS Lett. 2000 Jan 28;466(2-3):283-6
10682844
Curr Opin Chem Biol. 2008 Apr;12(2):151-8
18284924
Fold Des. 1998;3(6):497-512
9889159
Nucleic Acids Res. 2009 Jan;37(Database issue):D26-31
18940867
Curr Opin Struct Biol. 2003 Feb;13(1):110-4
12581667
Proc Natl Acad Sci U S A. 2009 Jul 7;106(27):11079-84
19541617
Nat Chem Biol. 2009 Aug;5(8):521-5
19620987
Methods Enzymol. 1996;266:554-71
8743706
Nucleic Acids Res. 2003 Jan 15;31(2):683-9
12527777
Adv Protein Chem. 1952;7:1-67
14933251
J Mol Biol. 2007 Oct 5;372(5):1261-77
17727879