title: Control of DNA minor groove width and Fis protein binding by the purine 2-amino group.
abstract: The width of the DNA minor groove varies with sequence and can be a major determinant of DNA shape recognition by proteins. For example, the minor groove within the center of the Fis-DNA complex narrows to about half the mean minor groove width of canonical B-form DNA to fit onto the protein surface. G/C base pairs within this segment, which is not contacted by the Fis protein, reduce binding affinities up to 2000-fold over A/T-rich sequences. We show here through multiple X-ray structures and binding properties of Fis-DNA complexes containing base analogs that the 2-amino group on guanine is the primary molecular determinant controlling minor groove widths. Molecular dynamics simulations of free-DNA targets with canonical and modified bases further demonstrate that sequence-dependent narrowing of minor groove widths is modulated almost entirely by the presence of purine 2-amino groups. We also provide evidence that protein-mediated phosphate neutralization facilitates minor groove compression and is particularly important for binding to non-optimally shaped DNA duplexes.
authors: Department of Biological Chemistry, David Geffen School of Medicine at the University of California at Los Angeles, Los Angeles, CA 90095-1737, USA.
authors: Stephen P
authors: SP
authors: Hancock
authors: Tahereh
authors: T
authors: Ghane
authors: Duilio
authors: D
authors: Cascio
authors: Remo
authors: R
authors: Rohs
authors: Rosa
authors: R
authors: Di Felice
authors: Reid C
authors: RC
authors: Johnson
mesh_terms: D020029:Base Pairing; D004247:DNA / Q000737:chemistry* / Q000378:metabolism; D035021:Factor For Inversion Stimulation Protein / Q000737:chemistry* / Q000378:metabolism; D056004:Molecular Dynamics Simulation; D009690:Nucleic Acid Conformation; D010710:Phosphates / Q000737:chemistry; D011485:Protein Binding; D011687:Purines / Q000737:chemistry
chemical_list: D035021:Factor For Inversion Stimulation Protein; D010710:Phosphates; D011687:Purines; D004247:DNA
references: J Mol Biol. 2006 Dec 8;364(4):777-98
references: 17045294
references: Biopolymers. 2003 May;69(1):144-58
references: 12717729
references: Cell. 2007 Nov 2;131(3):530-43
references: 17981120
references: Q Rev Biophys. 2009 Feb;42(1):41-81
references: 19508739
references: Biophys J. 2001 Jan;80(1):455-68
references: 11159416
references: Science. 1996 Mar 1;271(5253):1247-54
references: 8638105
references: J Biol Chem. 2000 Oct 6;275(40):31245-54
references: 10906136
references: Nucleic Acids Res. 2002 Aug 15;30(16):3615-23
references: 12177304
references: J Biomol Struct Dyn. 1989 Feb;6(4):655-67
references: 2619933
references: Annu Rev Biophys Biomol Struct. 2000;29:497-521
references: 10940257
references: Genes Dev. 2010 Apr 15;24(8):814-26
references: 20395367
references: Nat Prod Rep. 2001 Jun;18(3):291-309
references: 11476483
references: J Am Chem Soc. 2007 Nov 28;129(47):14739-45
references: 17985896
references: Biochemistry. 1993 Feb 9;32(5):1373-89
references: 8448146
references: Curr Opin Struct Biol. 2001 Jun;11(3):293-301
references: 11406377
references: Acta Crystallogr D Biol Crystallogr. 1997 May 1;53(Pt 3):240-55
references: 15299926
references: Nucleic Acids Res. 2001 Jul 1;29(13):2860-74
references: 11433033
references: Proc Natl Acad Sci U S A. 1976 Mar;73(3):804-8
references: 1062791
references: J Mol Biol. 2008 Jul 4;380(2):327-39
references: 18514225
references: Nucleic Acids Res. 2001 Jun 15;29(12):2522-34
references: 11410660
references: J Am Chem Soc. 2004 Dec 1;126(47):15330-1
references: 15563130
references: Nucleic Acids Res. 2003 Sep 1;31(17):5108-21
references: 12930962
references: Biophys J. 2007 Jun 1;92(11):3817-29
references: 17351000
references: Nucleic Acids Res. 2011 Mar;39(6):2073-91
references: 21097887
references: Nucleic Acids Res. 1997 Dec 15;25(24):4994-5002
references: 9396807
references: J Mol Biol. 2001 Oct 5;312(5):1037-49
references: 11580248
references: J Phys Chem B. 2012 Sep 6;116(35):10693-702
references: 22866829
references: Genome Res. 2008 Jun;18(6):900-10
references: 18340041
references: Biochemistry. 2008 Feb 26;47(8):2325-38
references: 18237194
references: Science. 1994 Nov 4;266(5186):763-70
references: 7973627
references: Annu Rev Biophys Biomol Struct. 1998;27:105-31
references: 9646864
references: Nucleic Acids Res. 1998 Oct 1;26(19):4309-14
references: 9742229
references: Nucleic Acids Res. 2008 Apr;36(7):2379-94
references: 18299282
references: Nature. 2009 Oct 29;461(7268):1248-53
references: 19865164
references: Adv Appl Microbiol. 2009;67:47-64
references: 19245936
references: J Comput Chem. 2005 Dec;26(16):1781-802
references: 16222654
references: Nature. 1991 Jan 10;349(6305):178-80
references: 1986310
references: Annu Rev Biochem. 2010;79:233-69
references: 20334529
references: J Mol Biol. 1991 Jan 5;217(1):177-99
references: 1988677
references: Trends Biochem Sci. 2012 Dec;37(12):553-62
references: 23153957
references: Curr Opin Struct Biol. 1999 Jun;9(3):298-304
references: 10361089
references: J Mol Biol. 2003 Jul 11;330(3):493-502
references: 12842466
references: Science. 1988 Nov 11;242(4880):899-907
references: 3187531
references: Curr Opin Genet Dev. 2005 Oct;15(5):507-14
references: 16099644
references: Nature. 1992 Jan 2;355(6355):89-91
references: 1731202
references: Acta Crystallogr D Biol Crystallogr. 2002 Nov;58(Pt 11):1948-54
references: 12393927
references: Nature. 1980 Oct 23;287(5784):755-8
references: 7432492
references: ACS Chem Biol. 2011 Dec 16;6(12):1314-20
references: 21967305
references: J Mol Biol. 1996 Dec 13;264(4):675-95
references: 8980678
references: J Mol Biol. 2010 Mar 5;396(4):1145-64
references: 20053356
references: Annu Rev Biophys Biomol Struct. 2002;31:343-60
references: 11988474
references: J Mol Biol. 2008 Feb 22;376(3):771-85
references: 18178221
references: Proc Natl Acad Sci U S A. 1991 Nov 1;88(21):9558-62
references: 1946369
references: Mol Microbiol. 1992 Nov;6(22):3257-65
references: 1484481
references: J Appl Crystallogr. 2007 Aug 1;40(Pt 4):658-674
references: 19461840
references: Nature. 1988 Sep 22;335(6188):321-9
references: 3419502
references: Nucleic Acids Res. 1992 Oct 25;20(20):5457-64
references: 1437563
references: Proc Natl Acad Sci U S A. 1998 Sep 15;95(19):11163-8
references: 9736707
references: Nucleic Acids Res. 2011 Aug;39(14):6269-76
references: 21478164
references: J Biol Chem. 2003 Apr 11;278(15):12955-60
references: 12569094
references: Proc Natl Acad Sci U S A. 2000 Jan 18;97(2):629-33
references: 10639130
references: Proc Natl Acad Sci U S A. 2011 Jun 28;108(26):10690-5
references: 21673140