title: Why Hofmeister effects of many salts favor protein folding but not DNA helix formation.
abstract: 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.
authors.affiliation: Department of Biochemistry, University of Wisconsin-Madison, Madison, WI 53706, USA. Impegram@wisc.edu
authors.forename: Laurel M
authors.initials: LM
authors.lastname: Pegram
authors.forename: Timothy
authors.initials: T
authors.lastname: Wendorff
authors.forename: Robert
authors.initials: R
authors.lastname: Erdmann
authors.forename: Irina
authors.initials: I
authors.lastname: Shkel
authors.forename: Dana
authors.initials: D
authors.lastname: Bellissimo
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Felitsky
authors.forename: M Thomas
authors.initials: MT
authors.lastname: Record
mesh_terms: 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
chemical_list: D006838:Hydrocarbons; D056968:Lac Repressors; D012492:Salts; D004247:DNA; D009584:Nitrogen; D010100:Oxygen
references.citation: Biochemistry. 1993 May 4;32(17):4604-8
references.pmid: 8387338
references.citation: J Phys Chem. 1967 May;71(6):1851-60
references.pmid: 6045721
references.citation: Curr Opin Chem Biol. 2006 Dec;10(6):658-63
references.pmid: 17035073
references.citation: Adv Protein Chem. 1998;51:355-432
references.pmid: 9615174
references.citation: J Phys Chem B. 2007 Aug 16;111(32):9675-85
references.pmid: 17658791
references.citation: J Am Chem Soc. 1972 Feb 23;94(4):1308-15
references.pmid: 5060274
references.citation: Biochemistry. 2009 Nov 3;48(43):10372-9
references.pmid: 19757837
references.citation: Adv Protein Chem. 1998;51:281-353
references.pmid: 9615173
references.citation: Proteins. 2000;Suppl 4:72-85
references.pmid: 11013402
references.citation: J Phys Chem B. 2007 May 17;111(19):5411-7
references.pmid: 17432897
references.citation: Protein Sci. 2001 Dec;10(12):2485-97
references.pmid: 11714916
references.citation: J Phys Chem B. 2008 Aug 7;112(31):9428-36
references.pmid: 18630860
references.citation: J Comput Chem. 2002 Apr 30;23(6):600-9
references.pmid: 11939594
references.citation: Biochemistry. 1991 Apr 30;30(17):4237-44
references.pmid: 2021617
references.citation: Biochemistry. 1981 Jun 23;20(13):3842-51
references.pmid: 7272280
references.citation: Biopolymers. 1969;7(4):557-70
references.pmid: 22442846
references.citation: Biopolymers. 1971;10(1):47-68
references.pmid: 5544944
references.citation: Biochemistry. 2003 Feb 25;42(7):2202-17
references.pmid: 12590610
references.citation: J Chem Phys. 2006 Jun 21;124(23):234905
references.pmid: 16821951
references.citation: Biochim Biophys Acta. 2006 Oct;1764(10):1546-52
references.pmid: 17015045
references.citation: Biochemistry. 1982 Dec 7;21(25):6545-52
references.pmid: 7150575
references.citation: Biochemistry. 1962 Jul;1:664-74
references.pmid: 13926683
references.citation: Science. 1964 Aug 7;145(3632):577-80
references.pmid: 14163781
references.citation: J Am Chem Soc. 1972 Feb 23;94(4):1299-308
references.pmid: 5060273
references.citation: Nucleic Acids Res. 2000 Jan 1;28(1):235-42
references.pmid: 10592235
references.citation: Biophys J. 2009 Nov 4;97(9):2595-603
references.pmid: 19883603
references.citation: Cell Biochem Biophys. 2008;50(1):1-22
references.pmid: 18043873
references.citation: Biochemistry. 2005 Dec 27;44(51):16896-911
references.pmid: 16363803
references.citation: Biophys J. 2006 Dec 15;91(12):4536-43
references.pmid: 17012314
references.citation: Biochemistry. 1973 Mar 27;12(7):1256-64
references.pmid: 4696753
references.citation: J Am Chem Soc. 2008 Sep 3;130(35):11582-3
references.pmid: 18686949
references.citation: Biophys J. 1996 Oct;71(4):2056-63
references.pmid: 8889180
references.citation: Angew Chem Int Ed Engl. 2001 Oct 15;40(20):3819-3821
references.pmid: 29712130
references.citation: BMC Bioinformatics. 2009 Apr 08;10:104
references.pmid: 19356231
references.citation: Arch Biochem Biophys. 2008 Nov 1;479(1):69-73
references.pmid: 18782555
references.citation: Science. 2004 Jul 16;305(5682):386-9
references.pmid: 15256668
references.citation: J Am Chem Soc. 1971 Dec 15;93(25):6787-93
references.pmid: 5133091
references.citation: Biochemistry. 2004 Nov 23;43(46):14732-43
references.pmid: 15544344
references.citation: Biochemistry. 2006 Apr 25;45(16):5190-205
references.pmid: 16618108
references.citation: Biochemistry. 1973 Mar 27;12(7):1264-71
references.pmid: 4348829
references.citation: Biochim Biophys Acta. 1996 Oct 17;1297(2):171-81
references.pmid: 8917619
references.citation: Science. 2003 Jul 18;301(5631):347-9
references.pmid: 12869755
references.citation: Proc Natl Acad Sci U S A. 2005 Nov 22;102(47):17002-7
references.pmid: 16284250
references.citation: Chem Phys Lett. 2008 Dec;467(1-3):1-8
references.pmid: 23750042
references.citation: Biochemistry. 1999 Jun 29;38(26):8409-22
references.pmid: 10387087
references.citation: Proc Natl Acad Sci U S A. 2006 Sep 26;103(39):14278-81
references.pmid: 16980410