The effect of charge-charge interactions on the kinetics of alpha-helix formation.
The formation of the monomeric alpha-helix represents one of the simplest scenarios in protein folding; however, our current understanding of the folding dynamics of the alpha-helix motif is mainly based on studies of alanine-rich model peptides. To examine the effect of peptide sequence on the folding kinetics of alpha-helices, we studied the relaxation kinetics of a 21-residue helical peptide, Conantokin-T (Con-T), using time-resolved infrared spectroscopy in conjunction with a laser-induced temperature jump technique. Con-T is a neuroactive peptide containing a large number of charged residues that is found in the venom of the piscivorous cone snail Conus tulipa . The temperature-jump relaxation kinetics of Con-T is distinctly slower than that of previously studied alanine-based peptides, suggesting that the folding time of alpha-helices is sequence-dependent. Furthermore, it appears that the slower folding of Con-T can be attributed to the fact that its helical conformation is stabilized by charge-charge interactions or salt bridges. Although this finding contradicts an earlier molecular dynamics simulation, it also has implications for existing models of protein folding.
Du
Deguo
D
Department of Chemistry, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Bunagan
Michelle R
MR
Gai
Feng
F
D000595:Amino Acid Sequence; D003198:Computer Simulation; D020916:Conotoxins; D036341:Intercellular Signaling Peptides and Proteins; D008956:Models, Chemical; D008958:Models, Molecular; D008969:Molecular Sequence Data; D008978:Mollusk Venoms / Q000737:chemistry*; D010455:Peptides / Q000737:chemistry*; D011487:Protein Conformation; D017510:Protein Folding; D020539:Sequence Analysis, Protein / Q000379:methods*; D055672:Static Electricity; D013329:Structure-Activity Relationship
D020916:Conotoxins; D036341:Intercellular Signaling Peptides and Proteins; D008978:Mollusk Venoms; D010455:Peptides; C063571:conantokin-T
Proc Natl Acad Sci U S A. 1999 Aug 3;96(16):9068-73
10430896
Proc Natl Acad Sci U S A. 1999 Oct 26;96(22):12524-9
10535955
Proteins. 2001 Jan 1;42(1):77-84
11093262
J Am Chem Soc. 2001 Sep 26;123(38):9235-8
11562202
J Am Chem Soc. 2001 Dec 5;123(48):12111-2
11724630
Proc Natl Acad Sci U S A. 2002 Mar 5;99(5):2788-93
11867741
Cell. 2002 Feb 22;108(4):573-82
11909527
Biopolymers. 2003 Jan;68(1):63-75
12579580
Biopolymers. 2003 Jan;68(1):91-109
12579582
Biophys J. 2003 Nov;85(5):3187-93
14581218
J Am Chem Soc. 2003 Dec 17;125(50):15388-94
14664583
Proc Natl Acad Sci U S A. 2003 Dec 23;100(26):15486-91
14671331
J Mol Biol. 2004 Mar 5;336(5):989-96
15037063
J Mol Biol. 2004 May 7;338(4):827-37
15099748
Curr Opin Struct Biol. 2004 Feb;14(1):76-88
15102453
J Mol Biol. 2004 Aug 20;341(4):1109-24
15328620
J Mol Biol. 1992 Feb 20;223(4):1121-38
1538392
Proc Natl Acad Sci U S A. 2004 Nov 9;101(45):15915-20
15520391
Biophys J. 2005 Apr;88(4):2472-93
15665128
Proc Natl Acad Sci U S A. 2005 Feb 15;102(7):2379-84
15699340
Proc Natl Acad Sci U S A. 2005 May 24;102(21):7517-22
15894611
Chem Commun (Camb). 2005 Dec 28;(48):5985-7
16333502
J Phys Chem B. 2006 Mar 2;110(8):3759-63
16494434
Biochemistry. 2006 Apr 4;45(13):4153-63
16566589
J Mol Biol. 2006 Jun 9;359(3):546-53
16643946
J Phys Chem B. 2005 Oct 27;109(42):19980-6
16853583
Biochemistry. 2006 Sep 12;45(36):10981-6
16953584
Methods Mol Biol. 2007;350:1-20
16957314
J Phys Chem B. 2006 Oct 19;110(41):20555-61
17034243
Biochemistry. 2006 Nov 7;45(44):13131-9
17073435
J Mol Biol. 1992 Jan 5;223(1):343-50
1731079
J Phys Chem B. 2007 May 3;111(17):4596-602
17419612
Science. 1990 Jul 20;249(4966):257-63
2165278
J Biol Chem. 1990 Apr 15;265(11):6025-9
2180939
J Mol Biol. 1990 Dec 20;216(4):1031-44
2266554
J Phys Chem B. 2004 Sep 30;108(39):null
24307864
J Chem Theory Comput. 2006 May;2(3):674-84
26626673
Proc Natl Acad Sci U S A. 1989 Jul;86(14):5286-90
2748584
Biochemistry. 1987 Dec 29;26(26):8508-12
3442672
Proc Natl Acad Sci U S A. 1995 Nov 21;92(24):10869-73
7479900
Biochemistry. 1995 Jul 11;34(27):8771-9
7612617
Biochemistry. 1993 Sep 21;32(37):9668-76
8373771
Biochemistry. 1996 Jan 23;35(3):691-7
8547249
Proc Natl Acad Sci U S A. 1996 Apr 2;93(7):2629-34
8610092
Biochemistry. 1996 May 28;35(21):6786-94
8639630
J Biol Chem. 1997 Jan 24;272(4):2291-9
8999936
J Biol Chem. 1997 Jan 17;272(3):1413-6
9019474
FEBS Lett. 1997 Apr 28;407(2):243-8
9166908
Biochemistry. 1997 Jul 8;36(27):8413-21
9204889
Nature. 1997 Nov 13;390(6656):196-9
9367160