Detection and architecture of small heat shock protein monomers.
BACKGROUND
Small Heat Shock Proteins (sHSPs) are chaperone-like proteins involved in the prevention of the irreversible aggregation of misfolded proteins. Although many studies have already been conducted on sHSPs, the molecular mechanisms and structural properties of these proteins remain unclear. Here, we propose a better understanding of the architecture, organization and properties of the sHSP family through structural and functional annotations. We focused on the Alpha Crystallin Domain (ACD), a sandwich fold that is the hallmark of the sHSP family.


RESULTS
We developed a new approach for detecting sHSPs and delineating ACDs based on an iterative Hidden Markov Model algorithm using a multiple alignment profile generated from structural data on ACD. Using this procedure on the UniProt databank, we found 4478 sequences identified as sHSPs, showing a very good coverage with the corresponding PROSITE and Pfam profiles. ACD was then delimited and structurally annotated. We showed that taxonomic-based groups of sHSPs (animals, plants, bacteria) have unique features regarding the length of their ACD and, more specifically, the length of a large loop within ACD. We detailed highly conserved residues and patterns specific to the whole family or to some groups of sHSPs. For 96% of studied sHSPs, we identified in the C-terminal region a conserved I/V/L-X-I/V/L motif that acts as an anchor in the oligomerization process. The fragment defined from the end of ACD to the end of this motif has a mean length of 14 residues and was named the C-terminal Anchoring Module (CAM).


CONCLUSIONS
This work annotates structural components of ACD and quantifies properties of several thousand sHSPs. It gives a more accurate overview of the architecture of sHSP monomers.
Poulain
Pierre
P
DSIMB, Inserm UMR-S 665 and Université Paris Diderot-Paris 7, INTS, Paris, France. pierre.poulain@univ-paris-diderot.fr
Gelly
Jean-Christophe
JC
Flatters
Delphine
D
D000465:Algorithms; D020816:Amino Acid Motifs; D019295:Computational Biology / Q000379:methods; D017124:Conserved Sequence; D030562:Databases, Protein; D050888:Heat-Shock Proteins, Small / Q000737:chemistry*; D011487:Protein Conformation; D016415:Sequence Alignment
D050888:Heat-Shock Proteins, Small
Nature. 1998 Aug 6;394(6693):595-9
9707123
Mol Vis. 2004 Sep 08;10:655-62
15448619
BMC Bioinformatics. 2007 Nov 09;8:435
17999748
Biochemistry. 2008 Jul 8;47(27):7001-11
18557634
Cell Stress Chaperones. 2003 Spring;8(1):62-9
12820655
Biochemistry. 2007 Aug 21;46(33):9605-14
17655279
J Mol Biol. 2009 Oct 9;392(5):1242-52
19646995
Eur J Biochem. 2000 Apr;267(7):1923-32
10727931
Biochemistry. 2002 Oct 15;41(41):12421-6
12369832
FEBS J. 2005 Jun;272(11):2613-27
15943797
Cell Mol Life Sci. 2005 Nov;62(21):2460-76
16143830
J Biol Chem. 2000 Feb 11;275(6):3767-71
10660525
BMC Bioinformatics. 2006 Sep 14;7:410
16970830
Biochem Biophys Res Commun. 2007 Feb 23;353(4):1115-20
17207466
Curr Opin Struct Biol. 2000 Feb;10(1):52-9
10679464
Eur J Biochem. 1994 Oct 1;225(1):1-19
7925426
Microbiol Mol Biol Rev. 2002 Mar;66(1):64-93; table of contents
11875128
J Biol Chem. 2006 Dec 29;281(52):40420-8
17079234
Cell Stress Chaperones. 2006 Summer;11(2):187-97
16817325
Proc Natl Acad Sci U S A. 1992 Nov 1;89(21):10449-53
1438232
J Biol Chem. 1999 Aug 20;274(34):24137-41
10446186
J Biol Chem. 1988 Apr 15;263(11):5141-9
3356684
Mol Biol Evol. 1993 Jan;10(1):103-26
8450753
Proteins. 2008 May 1;71(2):771-82
17979194
J Biol Chem. 1993 Jan 25;268(3):1517-20
8093612
Nucleic Acids Res. 2004 Jul 1;32(Web Server issue):W37-40
15215345
FEBS Lett. 2007 Jul 31;581(19):3665-74
17467701
Proc Natl Acad Sci U S A. 1999 Dec 7;96(25):14394-9
10588716
J Mol Biol. 1982 May 5;157(1):105-32
7108955
Biochemistry. 2006 Mar 7;45(9):3069-76
16503662
Structure. 2006 Jul;14(7):1197-204
16843901
Cell Stress Chaperones. 2009 Jan;14(1):105-11
18663603
Acta Crystallogr Sect F Struct Biol Cryst Commun. 2006 May 1;62(Pt 5):446-8
16682772
Nat Struct Biol. 2001 Dec;8(12):1025-30
11702068
FEBS Lett. 1992 Oct 19;311(2):143-9
1397302
Biochemistry (Mosc). 2006;71 Suppl 1:S83-90
16487074
Cell Stress Chaperones. 2008 Summer;13(2):183-97
18369739
Nucleic Acids Res. 2008 Jan;36(Database issue):D245-9
18003654
Genome Res. 2004 Jun;14(6):1188-90
15173120
Nucleic Acids Res. 2008 Jan;36(Database issue):D281-8
18039703
Int J Biol Macromol. 1998 May-Jun;22(3-4):151-62
9650070
Nat Genet. 1998 Sep;20(1):92-5
9731540
J Mol Biol. 1999 Nov 26;294(2):561-77
10610780
BMC Bioinformatics. 2009 Oct 15;10:335
19832975
Bioinformatics. 2009 May 1;25(9):1189-91
19151095
Nucleic Acids Res. 2009 Jan;37(Database issue):D169-74
18836194
Bioinformatics. 1998;14(9):755-63
9918945
J Mol Biol. 2005 Oct 14;353(1):68-79
16165157
Nat Struct Mol Biol. 2005 Oct;12(10):842-6
16205709
Biopolymers. 1983 Dec;22(12):2577-637
6667333
J Mol Evol. 1992 Dec;35(6):537-45
1474606
J Bacteriol. 1999 Jan;181(1):83-90
9864316
Biochemistry. 2009 May 12;48(18):3828-37
19323523
Cell Stress Chaperones. 2003 Spring;8(1):53-61
12820654
Proc Natl Acad Sci U S A. 2009 Sep 15;106(37):15604-9
19717454
J Biol Chem. 2005 Sep 30;280(39):33419-25
16046399