Structural analysis of protein folding by the long-chain archaeal chaperone FKBP26.
In the cell, protein folding is mediated by folding catalysts and chaperones. The two functions are often linked, especially when the catalytic module forms part of a multidomain protein, as in Methanococcus jannaschii peptidyl-prolyl cis/trans isomerase FKBP26. Here, we show that FKBP26 chaperone activity requires both a 50-residue insertion in the catalytic FKBP domain, also called 'Insert-in-Flap' or IF domain, and an 80-residue C-terminal domain. We determined FKBP26 structures from four crystal forms and analyzed chaperone domains in light of their ability to mediate protein-protein interactions. FKBP26 is a crescent-shaped homodimer. We reason that folding proteins are bound inside the large crescent cleft, thus enabling their access to inward-facing peptidyl-prolyl cis/trans isomerase catalytic sites and ipsilateral chaperone domain surfaces. As these chaperone surfaces participate extensively in crystal lattice contacts, we speculate that the observed lattice contacts reflect a proclivity for protein associations and represent substrate interactions by FKBP26 chaperone domains. Finally, we find that FKBP26 is an exceptionally flexible molecule, suggesting a mechanism for nonspecific substrate recognition.
Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10032, USA.
Erik
E
Martinez-Hackert
Wayne A
WA
Hendrickson
D019843:Archaeal Proteins / Q000737:chemistry* / Q000378:metabolism; D001665:Binding Sites; D002384:Catalysis; D017017:Methanococcus / Q000201:enzymology*; D008958:Models, Molecular; D018832:Molecular Chaperones / Q000737:chemistry* / Q000378:metabolism; D019696:Peptidylprolyl Isomerase / Q000737:chemistry* / Q000378:metabolism; D017510:Protein Folding; D017434:Protein Structure, Tertiary; D013499:Surface Properties
D019843:Archaeal Proteins; D018832:Molecular Chaperones; D019696:Peptidylprolyl Isomerase
Science. 1996 Jun 14;272(5268):1606-14
8658133
J Biomol NMR. 2007 Jun;38(2):161-4
17431550
Gene. 2000 Oct 3;256(1-2):319-26
11054562
Biochim Biophys Acta. 2010 Jun;1803(6):650-61
20132842
Eur J Biochem. 2002 Sep;269(18):4516-23
12230563
Nat Struct Mol Biol. 2009 Oct;16(10):1006-8
19809489
Proc Natl Acad Sci U S A. 2009 Dec 1;106(48):20282-7
19920179
Curr Top Med Chem. 2003;3(12):1315-47
12871165
Chem Rev. 2006 May;106(5):1917-30
16683761
J Bacteriol. 2004 Jun;186(12):3777-84
15175291
FEBS Lett. 2001 Oct 5;506(2):108-12
11591381
Science. 1991 May 10;252(5007):839-42
1709302
FEBS Lett. 1997 Apr 28;407(2):184-90
9166896
Nat Struct Biol. 2000 Mar;7(3):196-9
10700276
Acta Crystallogr D Biol Crystallogr. 2004 Dec;60(Pt 12 Pt 1):2256-68
15572779
Acta Crystallogr D Biol Crystallogr. 1994 Sep 1;50(Pt 5):760-3
15299374
J Mol Biol. 2003 May 16;328(5):1149-60
12729748
Appl Microbiol Biotechnol. 2004 Mar;64(1):99-105
14564491
J Synchrotron Radiat. 2004 Jan 1;11(Pt 1):49-52
14646132
Eur J Biochem. 2000 Jun;267(11):3139-49
10824098
Acta Crystallogr D Biol Crystallogr. 1997 May 1;53(Pt 3):240-55
15299926
Science. 2002 Mar 8;295(5561):1852-8
11884745
Acta Crystallogr D Biol Crystallogr. 1998 Sep 1;54(Pt 5):905-21
9757107
Front Biosci. 2000 Sep 01;5:D821-36
10966874
Nature. 2004 Sep 30;431(7008):590-6
15334087
Front Biosci. 2004 May 01;9:1680-720
14977579
J Mol Biol. 2007 May 18;368(5):1458-68
17397867
J Biol Chem. 2001 Oct 5;276(40):37034-41
11473108
Protein Eng. 1999 Sep;12(9):713-20
10506280
Proteins. 1996 Oct;26(2):192-203
8916227
Acta Crystallogr D Biol Crystallogr. 2001 Jan;57(Pt 1):122-33
11134934
J Biol Chem. 1994 Mar 11;269(10):7764-71
7907332
Structure. 2008 Aug 6;16(8):1153-5
18682216
Methods Enzymol. 1997;277:505-24
18488322
Curr Opin Struct Biol. 2000 Feb;10(1):40-5
10679456
J Mol Biol. 2004 Jan 9;335(2):595-608
14672666
Acta Crystallogr A. 1991 Mar 1;47 ( Pt 2):110-9
2025413
J Mol Biol. 2004 Feb 27;336(4):943-55
15095871
J Biol Chem. 2004 Apr 2;279(14):14165-70
14729669
Appl Environ Microbiol. 2002 Feb;68(2):464-9
11823179
J Mol Biol. 1997 Sep 5;271(5):827-37
9299330
Proteins. 1995 Dec;23(4):580-7
8749854
Acta Crystallogr D Biol Crystallogr. 2007 Apr;63(Pt 4):536-47
17372359
Gene. 2002 Jun 12;292(1-2):57-63
12119099
Proc Natl Acad Sci U S A. 1994 Oct 25;91(22):10370-4
7937957
Cell. 2009 Sep 4;138(5):923-34
19737520
J Biol Chem. 2010 Sep 3;285(36):27911-23
20595383
Nature. 1987 Aug 27-Sep 2;328(6133):834-6
3627230
Biochemistry. 2000 Mar 14;39(10):2822
10704235
J Mol Biol. 2009 Mar 27;387(2):295-305
19356587
Trends Biochem Sci. 1989 Aug;14(8):339-42
2572080
Cell Mol Life Sci. 2006 Dec;63(24):2889-900
17075696
EMBO J. 1990 May;9(5):1665-72
2184035
J Mol Biol. 2010 May 7;398(3):375-90
20230833
Nat Struct Biol. 1999 May;6(5):458-63
10331874
Biochemistry. 2006 Oct 3;45(39):11983-91
17002297