The CATH hierarchy revisited-structural divergence in domain superfamilies and the continuity of fold space.
This paper explores the structural continuum in CATH and the extent to which superfamilies adopt distinct folds. Although most superfamilies are structurally conserved, in some of the most highly populated superfamilies (4% of all superfamilies) there is considerable structural divergence. While relatives share a similar fold in the evolutionary conserved core, diverse elaborations to this core can result in significant differences in the global structures. Applying similar protocols to examine the extent to which structural overlaps occur between different fold groups, it appears this effect is confined to just a few architectures and is largely due to small, recurring super-secondary motifs (e.g., alphabeta-motifs, alpha-hairpins). Although 24% of superfamilies overlap with superfamilies having different folds, only 14% of nonredundant structures in CATH are involved in overlaps. Nevertheless, the existence of these overlaps suggests that, in some regions of structure space, the fold universe should be seen as more continuous.
Cuff
Alison
A
Institute of Structural and Molecular Biology, University College London, London, UK. cuff@biochem.ucl.ac.uk
Redfern
Oliver C
OC
Greene
Lesley
L
Sillitoe
Ian
I
Lewis
Tony
T
Dibley
Mark
M
Reid
Adam
A
Pearl
Frances
F
Dallman
Tim
T
Todd
Annabel
A
Garratt
Richard
R
Thornton
Janet
J
Orengo
Christine
C
D019295:Computational Biology / Q000379:methods; D030562:Databases, Protein; D008958:Models, Molecular; D017510:Protein Folding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000737:chemistry* / Q000145:classification
D011506:Proteins
J Mol Biol. 1995 Apr 7;247(4):536-40
7723011
Annu Rev Biochem. 2005;74:867-900
15954844
J Struct Biol. 2001 May-Jun;134(2-3):167-85
11551177
Proc Natl Acad Sci U S A. 2005 Jan 11;102(2):373-8
15630082
Bioinformatics. 2003 Jul 1;19(10):1275-83
12835272
Nucleic Acids Res. 2006 Feb 15;34(3):1066-80
16481312
Nucleic Acids Res. 2007 Jan;35(Database issue):D308-13
17098927
Structure. 1997 Aug 15;5(8):1093-108
9309224
Bioinformatics. 2001 Feb;17(2):200-1
11238081
J Mol Biol. 2003 Feb 7;326(1):317-36
12547212
Proteins. 2005 May 15;59(3):603-15
15768405
Curr Opin Struct Biol. 2008 Apr;18(2):170-7
18328690
Structure. 1993 Oct 15;1(2):105-20
8069624
Bioinformatics. 2007 Sep 15;23(18):2353-60
17709341
Bioinformatics. 2001 Jan;17(1):63-72
11222263
J Mol Biol. 2005 Mar 4;346(4):1173-88
15701525
Genome Biol. 2004;5(5):107
15128436
Proteins. 2005 Jan 1;58(1):166-79
15521074
Nucleic Acids Res. 2004 Oct 14;32(18):5539-45
15486203
Genome Res. 2002 Mar;12(3):503-14
11875040
Bioinformatics. 2005 Apr 15;21(8):1308-10
15604105
PLoS Comput Biol. 2007 Nov;3(11):e237
18052542
BMC Evol Biol. 2005 Feb 03;5:10
15691378
Nucleic Acids Res. 2005 Jul 1;33(Web Server issue):W249-51
15980462
Nat Genet. 2000 May;25(1):25-9
10802651
EMBO J. 1986 Apr;5(4):823-6
3709526
Proteins. 2001 Feb 15;42(3):332-44
11151005
PLoS Comput Biol. 2007 Nov;3(11):e232
18052539
Protein Sci. 1998 Nov;7(11):2469-71
9828015
Nucleic Acids Res. 2007 Jan;35(Database issue):D291-7
17135200
J Mol Biol. 1976 Jul 25;105(1):75-95
186608
Bioinformatics. 2003 Sep 22;19(14):1748-59
14512345
Curr Biol. 1993 Mar;3(3):141-8
15335781
Nature. 1994 Dec 15;372(6507):631-4
7990952
Curr Opin Struct Biol. 2006 Jun;16(3):393-8
16678402
J Mol Biol. 2005 May 20;348(5):1235-60
15854658
Bioinformatics. 2008 Mar 15;24(6):870-1
18218654
J Mol Biol. 2006 Jul 14;360(3):725-41
16780872
J Struct Biol. 2001 May-Jun;134(2-3):191-203
11551179
Acta Crystallogr D Biol Crystallogr. 1998 Nov 1;54(Pt 6 Pt 1):1147-54
10089491
J Mol Biol. 2002 Nov 8;323(5):909-26
12417203