title: Structure of concatenated HAMP domains provides a mechanism for signal transduction.
abstract: HAMP domains are widespread prokaryotic signaling modules found as single domains or poly-HAMP chains in both transmembrane and soluble proteins. The crystal structure of a three-unit poly-HAMP chain from the Pseudomonas aeruginosa soluble receptor Aer2 defines a universal parallel four-helix bundle architecture for diverse HAMP domains. Two contiguous domains integrate to form a concatenated di-HAMP structure. The three HAMP domains display two distinct conformations that differ by changes in helical register, crossing angle, and rotation. These conformations are stabilized by different subsets of conserved residues. Known signals delivered to HAMP would be expected to switch the relative stability of the two conformations and the position of a coiled-coil phase stutter at the junction with downstream helices. We propose that the two conformations represent opposing HAMP signaling states and suggest a signaling mechanism whereby HAMP domains interconvert between the two states, which alternate down a poly-HAMP chain.
authors.affiliation: Department of Chemistry and Chemical Biology, Cornell University, Ithaca, NY 14853, USA.
authors.forename: Michael V
authors.initials: MV
authors.lastname: Airola
authors.forename: Kylie J
authors.initials: KJ
authors.lastname: Watts
authors.forename: Alexandrine M
authors.initials: AM
authors.lastname: Bilwes
authors.forename: Brian R
authors.initials: BR
authors.lastname: Crane
mesh_terms: D000595:Amino Acid Sequence; D019295:Computational Biology / Q000379:methods; D008958:Models, Molecular; D008968:Molecular Conformation; D008969:Molecular Sequence Data; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000737:chemistry; D011550:Pseudomonas aeruginosa / Q000378:metabolism*; D012645:Selenomethionine / Q000737:chemistry; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D012997:Solvents / Q000737:chemistry
chemical_list: D011506:Proteins; D012997:Solvents; D012645:Selenomethionine
references.citation: J Bacteriol. 2008 Oct;190(20):6676-85
references.pmid: 18621896
references.citation: Biochemistry. 2005 Feb 1;44(4):1268-77
references.pmid: 15667220
references.citation: EMBO J. 2001 Oct 1;20(19):5312-9
references.pmid: 11574462
references.citation: Trends Biochem Sci. 2008 Jan;33(1):9-19
references.pmid: 18165013
references.citation: Methods Enzymol. 1997;276:307-26
references.pmid: 27754618
references.citation: FEMS Microbiol Lett. 1999 Jul 1;176(1):111-6
references.pmid: 10418137
references.citation: Acta Crystallogr D Biol Crystallogr. 2000 Aug;56(Pt 8):965-72
references.pmid: 10944333
references.citation: Genome Res. 2004 Jun;14(6):1188-90
references.pmid: 15173120
references.citation: Biochemistry. 2009 Oct 6;48(39):9266-77
references.pmid: 19705835
references.citation: Proc Natl Acad Sci U S A. 2008 Oct 28;105(43):16555-60
references.pmid: 18940922
references.citation: J Bacteriol. 2010 Feb;192(3):734-45
references.pmid: 19966007
references.citation: Biochemistry. 2004 Feb 24;43(7):1763-70
references.pmid: 14967017
references.citation: J Struct Biol. 1999 Apr-May;125(2-3):156-65
references.pmid: 10222271
references.citation: Proc Natl Acad Sci U S A. 2009 Mar 3;106(9):3461-6
references.pmid: 19218451
references.citation: Nature. 2006 Mar 2;440(7080):115-9
references.pmid: 16452929
references.citation: Cell. 2006 Sep 8;126(5):929-40
references.pmid: 16959572
references.citation: Trends Biochem Sci. 2001 Apr;26(4):257-65
references.pmid: 11295559
references.citation: Acta Crystallogr D Biol Crystallogr. 1998 Sep 1;54(Pt 5):905-21
references.pmid: 9757107
references.citation: Curr Opin Struct Biol. 2006 Aug;16(4):525-30
references.pmid: 16765587
references.citation: Mol Microbiol. 2009 Sep;73(5):801-14
references.pmid: 19656294
references.citation: Annu Rev Biochem. 2008;77:363-82
references.pmid: 18410248
references.citation: J Biol Chem. 2008 Oct 17;283(42):28691-701
references.pmid: 18697747
references.citation: J Bacteriol. 2008 Mar;190(6):2118-27
references.pmid: 18203838
references.citation: Mol Microbiol. 2002 May;44(3):709-19
references.pmid: 11994152
references.citation: Adv Protein Chem. 2005;70:37-78
references.pmid: 15837513
references.citation: Nucleic Acids Res. 1997 Sep 1;25(17):3389-402
references.pmid: 9254694
references.citation: J Biol Chem. 2003 Jun 20;278(25):22812-9
references.pmid: 12672798
references.citation: FEMS Microbiol Lett. 2004 Feb 16;231(2):247-52
references.pmid: 14987771
references.citation: Acta Crystallogr D Biol Crystallogr. 1999 Apr;55(Pt 4):849-61
references.pmid: 10089316
references.citation: J Bacteriol. 2003 Aug;185(16):4872-82
references.pmid: 12897007
references.citation: Curr Opin Struct Biol. 2007 Dec;17(6):706-15
references.pmid: 17913492
references.citation: Biochemistry. 2007 Dec 4;46(48):13684-95
references.pmid: 17994770
references.citation: Structure. 2009 Feb 13;17(2):190-201
references.pmid: 19217390
references.citation: Science. 1993 Dec 24;262(5142):2027-30
references.pmid: 8266097
references.citation: Biochemistry. 1998 Jul 28;37(30):10746-56
references.pmid: 9692965
references.citation: J Struct Biol. 2002 Jan-Feb;137(1-2):54-64
references.pmid: 12064933
references.citation: Mol Microbiol. 2007 Sep;65(6):1415-24
references.pmid: 17824925