Molecular dynamics simulations of cytochrome c unfolding in AOT reverse micelles: The first steps.
This paper explores the reduced form of horse cytochrome c confined in reverse micelles (RM) of sodium bis-(2-ethylhexyl) sulfosuccinate (AOT) in isooctane by molecular dynamics simulation. RMs of two sizes were constructed at a water content of W (o) = [ H₂O ]/[AOT] = 5.5 and 9.1. Our results show that the protein secondary structure and the heme conformation both depend on micellar hydration. At low hydration, the protein structure and the heme moiety remain stable, whereas at high water content the protein becomes unstable and starts to unfold. At W (o) = 9.1 , according to the X-ray structure, conformational changes are mainly localized on protein loops and around the heme moiety, where we observe a partial opening of the heme crevice. These findings suggest that within our time window (10ns), the structural changes observed at the heme level are the first steps of the protein denaturation process, previously described experimentally in micellar solutions. In addition, a specific binding of AOT molecules to a few lysine residues of the protein was found only in the small-sized RM.
Abel
S
S
DSV/iBiTecS/SB2SM, CNRS URA, Gif-sur-Yvette, France. stephane.abel@cea.fr
Waks
M
M
Marchi
M
M
D001665:Binding Sites; D045304:Cytochromes c / Q000737:chemistry*; D004143:Dioctyl Sulfosuccinic Acid / Q000737:chemistry*; D006418:Heme / Q000737:chemistry; D008823:Micelles; D056004:Molecular Dynamics Simulation; D011489:Protein Denaturation; D017433:Protein Structure, Secondary; D058767:Protein Unfolding; D012996:Solutions / Q000737:chemistry; D013997:Time Factors; D014867:Water / Q000737:chemistry
D008823:Micelles; D012996:Solutions; D014867:Water; D004143:Dioctyl Sulfosuccinic Acid; D006418:Heme; D045304:Cytochromes c
J Phys Chem B. 2009 Nov 12;113(45):15029-39
19842706
J Mol Graph. 1996 Feb;14(1):33-8, 27-8
8744570
Cell. 1996 Jul 12;86(1):147-57
8689682
Biochemistry. 1998 May 5;37(18):6402-9
9572857
J Biol Chem. 1989 Feb 5;264(4):2292-301
2536703
Biophys J. 2009 May 20;96(10):L57-9
19450460
J Chem Phys. 2008 Dec 28;129(24):244503
19123513
Proc Natl Acad Sci U S A. 2002 Feb 5;99(3):1329-34
11773620
Biochemistry. 1996 May 14;35(19):6058-63
8634247
J Am Chem Soc. 2003 Jun 11;125(23):6927-36
12783545
J Phys Chem B. 2008 May 1;112(17):5381-92
18410160
Chem Rev. 2005 Sep;105(9):3197-219
16159150
Science. 2002 Nov 29;298(5599):1722-3
12459570
J Phys Chem B. 2006 Jun 15;110(23):11504-10
16771426
Proc Natl Sci Counc Repub China B. 2000 Jul;24(3):89-100
10943941
Protein Sci. 2001 Feb;10(2):250-61
11266611
J Am Chem Soc. 2004 Aug 11;126(31):9498-9
15291527
J Am Chem Soc. 2008 Feb 13;130(6):1866-70
18198866
J Phys Chem B. 1998 Apr 30;102(18):3586-616
24889800
Eur J Biochem. 1987 Dec 1;169(2):259-68
2826140
Colloids Surf B Biointerfaces. 2004 Nov 15;38(3-4):179-85
15542322
J Am Chem Soc. 2006 Oct 4;128(39):12758-65
17002370
Langmuir. 2008 Jun 3;24(11):5714-25
18454560
J Phys Chem B. 2006 Mar 16;110(10):4978-84
16526739
Biochemistry. 1992 Feb 18;31(6):1636-43
1310614
J Comput Chem. 2010 Apr 15;31(5):1106-16
19824035
Langmuir. 2006 Oct 24;22(22):9112-20
17042518
J Colloid Interface Sci. 2006 May 1;297(1):276-83
16298384
Phys Rev E Stat Phys Plasmas Fluids Relat Interdiscip Topics. 1996 Apr;53(4):R3040-R3043
9964761
J Biol Chem. 1974 Mar 25;249(6):1988-90
4361834
J Mol Biol. 1990 Jul 20;214(2):585-95
2166170
J Colloid Interface Sci. 2006 Apr 1;296(1):356-64
16214159
Phys Rev E Stat Phys Plasmas Fluids Relat Interdiscip Topics. 2000 Jan;61(1):682-9
11046311
J Comput Chem. 2004 Oct;25(13):1613-22
15264255
Biochemistry. 1997 Oct 21;36(42):13122-32
9335575
J Am Chem Soc. 2006 Jan 18;128(2):382-3
16402804
J Phys Chem B. 2005 Sep 8;109(35):16891-900
16853150
J Phys Chem B. 2005 Apr 14;109(14):6732-40
16851757
Proteins. 1986 Sep;1(1):4-15
2453052
J Am Chem Soc. 2002 Jun 12;124(23):6787-91
12047201
J Mol Graph Model. 2006 Sep;25(1):77-86
16386443
J Am Chem Soc. 2004 Aug 25;126(33):10254-5
15315432
Biochemistry. 1989 Aug 8;28(16):6722-8
2551379
J Phys Chem B. 2005 Jan 13;109(1):471-9
16851038
Proteins. 1995 Dec;23(4):566-79
8749853
Faraday Discuss. 1996;(103):227-44
9136639
Proteins. 2006 Nov 15;65(3):702-11
16981201
J Phys Chem B. 2006 Jun 22;110(24):11615-9
16800453
Phys Chem Chem Phys. 2010 May 14;12(18):4694-703
20428549