title: A Miniature Protein Stabilized by a Cation-π Interaction Network.
abstract: The design of folded miniature proteins is predicated on establishing noncovalent interactions that direct the self-assembly of discrete thermostable tertiary structures. In this work, we describe how a network of cation-π interactions present in proteins containing "WSXWS motifs" can be emulated to stabilize the core of a miniature protein. This 19-residue protein sequence recapitulates a set of interdigitated arginine and tryptophan residues that stabilize a distinctive β-strand:loop:PPII-helix topology. Validation of the compact fold determined by NMR was carried out by mutagenesis of the cation-π network and by comparison to the corresponding disulfide-bridged structure. These results support the involvement of a coordinated set of cation-π interactions that stabilize the tertiary structure.
authors.affiliation: Department of Chemistry, New York University , 100 Washington Square East, New York, New York 10003, United States.|Department of Biology, Center for Genomics and Systems Biology, New York University , 12 Waverly Place, New York, New York 10003, United States.
authors.forename: Timothy W
authors.initials: TW
authors.lastname: Craven
authors.affiliation: Department of Chemistry, New York University , 100 Washington Square East, New York, New York 10003, United States.
authors.forename: Min-Kyu
authors.initials: MK
authors.lastname: Cho
authors.affiliation: Department of Chemistry, New York University , 100 Washington Square East, New York, New York 10003, United States.
authors.forename: Nathaniel J
authors.initials: NJ
authors.lastname: Traaseth
authors.affiliation: Department of Biology, Center for Genomics and Systems Biology, New York University , 12 Waverly Place, New York, New York 10003, United States.|Department of Computer Science, Courant Institute of Mathematical Sciences, New York University , New York, New York 10012, United States.|Simons Center for Data Analysis , New York, New York 10010, United States.
authors.forename: Richard
authors.initials: R
authors.lastname: Bonneau
authors.affiliation: Department of Chemistry, New York University , 100 Washington Square East, New York, New York 10003, United States.
authors.forename: Kent
authors.initials: K
authors.lastname: Kirshenbaum
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D002412:Cations / Q000737:chemistry*; D008969:Molecular Sequence Data; D019906:Nuclear Magnetic Resonance, Biomolecular; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000737:chemistry*; D016415:Sequence Alignment
chemical_list: D002412:Cations; D011506:Proteins
references.citation: Nat Struct Biol. 2002 Jun;9(6):425-30
references.pmid: 11979279
references.citation: EMBO J. 1998 Mar 16;17(6):1665-74
references.pmid: 9501088
references.citation: Structure. 2011 Dec 7;19(12):1864-75
references.pmid: 22153509
references.citation: Biochemistry. 2002 Jun 25;41(25):8152-61
references.pmid: 12069608
references.citation: J Am Chem Soc. 2015 Nov 11;137(44):14084-93
references.pmid: 26465072
references.citation: Science. 1996 Jan 12;271(5246):163-8
references.pmid: 8539615
references.citation: Proc Natl Acad Sci U S A. 1999 Aug 17;96(17):9459-64
references.pmid: 10449714
references.citation: Nature. 1998 Oct 1;395(6701):511-6
references.pmid: 9774108
references.citation: Genome Res. 2004 Jun;14(6):1188-90
references.pmid: 15173120
references.citation: Curr Protein Pept Sci. 2000 Dec;1(4):349-84
references.pmid: 12369905
references.citation: Protein Sci. 2006 Jan;15(1):74-83
references.pmid: 16373476
references.citation: Biochemistry. 2006 Dec 19;45(50):15000-10
references.pmid: 17154537
references.citation: J Am Chem Soc. 2008 Mar 12;130(10):2948-9
references.pmid: 18271592
references.citation: Biochemistry. 2004 May 18;43(19):5864-9
references.pmid: 15134460
references.citation: J Biol Chem. 2012 Mar 16;287(12):9454-60
references.pmid: 22235133
references.citation: J Am Chem Soc. 2013 May 8;135(18):6846-52
references.pmid: 23627648
references.citation: J Biol Chem. 2010 Mar 12;285(11):8422-33
references.pmid: 20053995
references.citation: Structure. 2012 Feb 8;20(2):270-82
references.pmid: 22325776
references.citation: Methods Enzymol. 2011;487:545-74
references.pmid: 21187238
references.citation: Nat Struct Biol. 2001 Jun;8(6):535-9
references.pmid: 11373623
references.citation: J Biol Chem. 1996 Mar 1;271(9):4699-708
references.pmid: 8617735
references.citation: Structure. 2004 Aug;12(8):1507-18
references.pmid: 15296744
references.citation: Science. 1998 Dec 11;282(5396):2088-92
references.pmid: 9851931
references.citation: J Am Chem Soc. 2007 Sep 12;129(36):11024-5
references.pmid: 17705497
references.citation: Blood. 2000 Apr 15;95(8):2491-8
references.pmid: 10753826
references.citation: Science. 1996 Jan 19;271(5247):342-5
references.pmid: 8553067
references.citation: Proc Natl Acad Sci U S A. 2007 Jul 31;104(31):12737-42
references.pmid: 17652170
references.citation: J Am Chem Soc. 2008 Nov 5;130(44):14675-83
references.pmid: 18842046
references.citation: J Am Chem Soc. 2002 Apr 3;124(13):3284-91
references.pmid: 11916412
references.citation: Structure. 2010 Mar 10;18(3):332-42
references.pmid: 20223216
references.citation: Science. 2005 Nov 18;310(5751):1159-63
references.pmid: 16293754
references.citation: Chem Biol. 2012 Jul 27;19(7):819-30
references.pmid: 22840770
references.citation: Proc Natl Acad Sci U S A. 2006 Feb 28;103(9):3135-40
references.pmid: 16492764
references.citation: Proc Natl Acad Sci U S A. 2002 Dec 10;99(25):15959-64
references.pmid: 12461182
references.citation: Nature. 1999 Oct 14;401(6754):713-7
references.pmid: 10537111
references.citation: Structure. 2012 Mar 7;20(3):487-97
references.pmid: 22405007
references.citation: Proc Natl Acad Sci U S A. 2001 May 8;98(10):5578-83
references.pmid: 11331745
references.citation: Mol Cell. 2008 Sep 5;31(5):737-48
references.pmid: 18775332
references.citation: J Mol Biol. 1993 Mar 20;230(2):543-74
references.pmid: 8464064
references.citation: J Am Chem Soc. 2006 Oct 4;128(39):12735-42
references.pmid: 17002367
references.citation: Nature. 2009 Mar 26;458(7237):534-7
references.pmid: 19252481
references.citation: Cell. 2008 Jan 25;132(2):259-72
references.pmid: 18243101
references.citation: J Magn Reson. 2003 Jan;160(1):65-73
references.pmid: 12565051
references.citation: Protein Sci. 2003 Nov;12(11):2443-52
references.pmid: 14573858
references.citation: Biochemistry. 2012 Jun 26;51(25):5041-51
references.pmid: 22667692
references.citation: Nature. 2006 May 18;441(7091):375-7
references.pmid: 16710424
references.citation: J Phys Chem B. 2006 Mar 2;110(8):3759-63
references.pmid: 16494434
references.citation: Science. 1998 Jul 10;281(5374):253-6
references.pmid: 9657719
references.citation: Angew Chem Int Ed Engl. 2000 Jul 3;39(13):2330-2333
references.pmid: 10941081