Why Hofmeister effects of many salts favor protein folding but not DNA helix formation.
The majority ( approximately 70%) of surface buried in protein folding is hydrocarbon, whereas in DNA helix formation, the majority ( approximately 65%) of surface buried is relatively polar nitrogen and oxygen. Our previous quantification of salt exclusion from hydrocarbon (C) accessible surface area (ASA) and accumulation at amide nitrogen (N) and oxygen (O) ASA leads to a prediction of very different Hofmeister effects on processes that bury mostly polar (N, O) surface compared to the range of effects commonly observed for processes that bury mainly nonpolar (C) surface, e.g., micelle formation and protein folding. Here we quantify the effects of salts on folding of the monomeric DNA binding domain (DBD) of lac repressor (lac DBD) and on formation of an oligomeric DNA duplex. In accord with this prediction, no salt investigated has a stabilizing Hofmeister effect on DNA helix formation. Our ASA-based analyses of model compound data and estimates of the surface area buried in protein folding and DNA helix formation allow us to predict Hofmeister effects on these processes. We observe semiquantitative to quantitative agreement between these predictions and the experimental values, obtained from a novel separation of coulombic and Hofmeister effects. Possible explanations of deviations, including salt-dependent unfolded ensembles and interactions with other types of surface, are discussed.
Pegram
Laurel M
LM
Department of Biochemistry, University of Wisconsin-Madison, Madison, WI 53706, USA. Impegram@wisc.edu
Wendorff
Timothy
T
Erdmann
Robert
R
Shkel
Irina
I
Bellissimo
Dana
D
Felitsky
Daniel J
DJ
Record
M Thomas
MT
D002942:Circular Dichroism; D004247:DNA / Q000737:chemistry*; D006838:Hydrocarbons / Q000737:chemistry; D056968:Lac Repressors / Q000378:metabolism; D008956:Models, Chemical; D009584:Nitrogen / Q000737:chemistry; D009690:Nucleic Acid Conformation / Q000187:drug effects*; D010100:Oxygen / Q000737:chemistry; D017510:Protein Folding / Q000187:drug effects*; D012492:Salts / Q000737:chemistry* / Q000494:pharmacology*; D013816:Thermodynamics
D006838:Hydrocarbons; D056968:Lac Repressors; D012492:Salts; D004247:DNA; D009584:Nitrogen; D010100:Oxygen
Biochemistry. 1993 May 4;32(17):4604-8
8387338
J Phys Chem. 1967 May;71(6):1851-60
6045721
Curr Opin Chem Biol. 2006 Dec;10(6):658-63
17035073
Adv Protein Chem. 1998;51:355-432
9615174
J Phys Chem B. 2007 Aug 16;111(32):9675-85
17658791
J Am Chem Soc. 1972 Feb 23;94(4):1308-15
5060274
Biochemistry. 2009 Nov 3;48(43):10372-9
19757837
Adv Protein Chem. 1998;51:281-353
9615173
Proteins. 2000;Suppl 4:72-85
11013402
J Phys Chem B. 2007 May 17;111(19):5411-7
17432897
Protein Sci. 2001 Dec;10(12):2485-97
11714916
J Phys Chem B. 2008 Aug 7;112(31):9428-36
18630860
J Comput Chem. 2002 Apr 30;23(6):600-9
11939594
Biochemistry. 1991 Apr 30;30(17):4237-44
2021617
Biochemistry. 1981 Jun 23;20(13):3842-51
7272280
Biopolymers. 1969;7(4):557-70
22442846
Biopolymers. 1971;10(1):47-68
5544944
Biochemistry. 2003 Feb 25;42(7):2202-17
12590610
J Chem Phys. 2006 Jun 21;124(23):234905
16821951
Biochim Biophys Acta. 2006 Oct;1764(10):1546-52
17015045
Biochemistry. 1982 Dec 7;21(25):6545-52
7150575
Biochemistry. 1962 Jul;1:664-74
13926683
Science. 1964 Aug 7;145(3632):577-80
14163781
J Am Chem Soc. 1972 Feb 23;94(4):1299-308
5060273
Nucleic Acids Res. 2000 Jan 1;28(1):235-42
10592235
Biophys J. 2009 Nov 4;97(9):2595-603
19883603
Cell Biochem Biophys. 2008;50(1):1-22
18043873
Biochemistry. 2005 Dec 27;44(51):16896-911
16363803
Biophys J. 2006 Dec 15;91(12):4536-43
17012314
Biochemistry. 1973 Mar 27;12(7):1256-64
4696753
J Am Chem Soc. 2008 Sep 3;130(35):11582-3
18686949
Biophys J. 1996 Oct;71(4):2056-63
8889180
Angew Chem Int Ed Engl. 2001 Oct 15;40(20):3819-3821
29712130
BMC Bioinformatics. 2009 Apr 08;10:104
19356231
Arch Biochem Biophys. 2008 Nov 1;479(1):69-73
18782555
Science. 2004 Jul 16;305(5682):386-9
15256668
J Am Chem Soc. 1971 Dec 15;93(25):6787-93
5133091
Biochemistry. 2004 Nov 23;43(46):14732-43
15544344
Biochemistry. 2006 Apr 25;45(16):5190-205
16618108
Biochemistry. 1973 Mar 27;12(7):1264-71
4348829
Biochim Biophys Acta. 1996 Oct 17;1297(2):171-81
8917619
Science. 2003 Jul 18;301(5631):347-9
12869755
Proc Natl Acad Sci U S A. 2005 Nov 22;102(47):17002-7
16284250
Chem Phys Lett. 2008 Dec;467(1-3):1-8
23750042
Biochemistry. 1999 Jun 29;38(26):8409-22
10387087
Proc Natl Acad Sci U S A. 2006 Sep 26;103(39):14278-81
16980410