title: Cold denaturation of a protein dimer monitored at atomic resolution.
abstract: Protein folding and unfolding are crucial for a range of biological phenomena and human diseases. Defining the structural properties of the involved transient species is therefore of prime interest. Using a combination of cold denaturation with NMR spectroscopy, we reveal detailed insight into the unfolding of the homodimeric repressor protein CylR2. Seven three-dimensional structures of CylR2 at temperatures from 25 °C to -16 °C reveal a progressive dissociation of the dimeric protein into a native-like monomeric intermediate followed by transition into a highly dynamic, partially folded state. The core of the partially folded state seems critical for biological function and misfolding.
authors: Department for NMR-based Structural Biology, Max Planck Institute for Biophysical Chemistry, Göttingen, Germany.
authors: Mariusz
authors: M
authors: Jaremko
authors: Łukasz
authors: Ł
authors: Jaremko
authors: Hai-Young
authors: HY
authors: Kim
authors: Min-Kyu
authors: MK
authors: Cho
authors: Charles D
authors: CD
authors: Schwieters
authors: Karin
authors: K
authors: Giller
authors: Stefan
authors: S
authors: Becker
authors: Markus
authors: M
authors: Zweckstetter
mesh_terms: D001426:Bacterial Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D001665:Binding Sites; D003080:Cold Temperature; D003603:Cytotoxins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D004269:DNA, Bacterial / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D013293:Enterococcus faecalis / Q000235:genetics / Q000378:metabolism*; D004926:Escherichia coli / Q000235:genetics; D008958:Models, Molecular; D008968:Molecular Conformation; D019906:Nuclear Magnetic Resonance, Biomolecular; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D011489:Protein Denaturation; D017510:Protein Folding; D055503:Protein Multimerization; D058767:Protein Unfolding; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D003603:Cytotoxins; D004269:DNA, Bacterial; D011994:Recombinant Proteins
references: Trends Biochem Sci. 1992 Aug;17(8):292-5
references: 1412703
references: Nat Rev Mol Cell Biol. 2008 Aug;9(8):650-4
references: 18578032
references: Biochemistry. 2003 Nov 4;42(43):12461-5
references: 14580191
references: Curr Opin Struct Biol. 2007 Feb;17(1):30-7
references: 17239580
references: J Mol Biol. 2007 Jan 19;365(3):870-80
references: 17109883
references: J Am Chem Soc. 2009 Jan 28;131(3):1025-36
references: 19115852
references: Protein Sci. 2003 Jan;12(1):66-72
references: 12493829
references: Proc Natl Acad Sci U S A. 2007 Oct 2;104(40):15717-22
references: 17898173
references: Methods Mol Biol. 1995;40:313-41
references: 7633528
references: Biophys J. 2011 May 4;100(9):L47-9
references: 21539772
references: Nature. 2002 Jan 3;415(6867):84-7
references: 11780122
references: Methods Mol Biol. 2004;278:233-54
references: 15317999
references: Proc Natl Acad Sci U S A. 2005 Apr 5;102(14):5026-31
references: 15793003
references: Biochemistry. 2001 Mar 27;40(12):3525-35
references: 11297418
references: Nat Struct Biol. 1997 Aug;4(8):630-4
references: 9253412
references: Proc Natl Acad Sci U S A. 2007 May 29;104(22):9272-7
references: 17517666
references: Chem Rev. 2004 Aug;104(8):3623-40
references: 15303831
references: Nature. 2004 Jul 29;430(6999):586-90
references: 15282609
references: Proc Natl Acad Sci U S A. 1994 Aug 16;91(17):8244-7
references: 8058788
references: Nat Struct Biol. 2002 Apr;9(4):308-15
references: 11887182
references: J Mol Biol. 2007 Feb 23;366(3):1001-15
references: 17188712
references: Crit Rev Biochem Mol Biol. 1990;25(4):281-305
references: 2225910
references: Nature. 2011 Aug 21;477(7362):111-4
references: 21857680
references: Nucleic Acids Res. 2006 Jul 1;34(Web Server issue):W63-9
references: 16845087
references: J Biol Chem. 1999 Nov 12;274(46):32943-9
references: 10551861
references: Proc Natl Acad Sci U S A. 2011 Jun 28;108(26):10532-7
references: 21670244
references: Science. 2011 Oct 28;334(6055):517-20
references: 22034434
references: Science. 1996 Nov 15;274(5290):1161-3
references: 8895458
references: Nature. 2001 Feb 1;409(6820):641-5
references: 11214326
references: Biophys J. 2009 Mar 18;96(6):2045-54
references: 19289032
references: Methods Mol Biol. 2004;278:353-78
references: 15318003
references: J Am Chem Soc. 2008 Nov 19;130(46):15318-26
references: 18939797
references: J Biol Chem. 2001 Jul 20;276(29):27207-13
references: 11306576
references: Proc Natl Acad Sci U S A. 2011 May 31;108(22):9078-83
references: 21562212
references: Nat Struct Mol Biol. 2004 Apr;11(4):352-7
references: 14990997
references: Methods Enzymol. 1989;177:86-121
references: 2558275
references: J Mol Biol. 2008 Dec 12;384(2):531-9
references: 18848567
references: Proc Natl Acad Sci U S A. 2007 Nov 20;104(47):18473-7
references: 18006656
references: J Mol Biol. 1996 Jun 21;259(4):805-18
references: 8683584
references: J Magn Reson. 2003 Jan;160(1):65-73
references: 12565051
references: Nature. 2005 Oct 13;437(7061):1053-6
references: 16222301
references: Nat Struct Mol Biol. 2009 Mar;16(3):318-24
references: 19252485
references: Biochem J. 2010 Jul 15;429(2):251-60
references: 20441567
references: Proteins. 2012 Jan;80(1):184-93
references: 22038766
references: J Struct Funct Genomics. 2011 Mar;12(1):1-7
references: 21533787
references: Science. 2012 Apr 20;336(6079):362-6
references: 22517863
references: Q Rev Biophys. 2007 Nov;40(4):287-326
references: 18405419
references: Science. 2010 Sep 10;329(5997):1312-6
references: 20829478