title: Structural analysis of the GGDEF-EAL domain-containing c-di-GMP receptor FimX.
abstract: Bacterial pathogenesis involves social behavior including biofilm formation and swarming, processes that are regulated by the bacterially unique second messenger cyclic di-GMP (c-di-GMP). Diguanylate cyclases containing GGDEF and phosphodiesterases containing EAL domains have been identified as the enzymes controlling cellular c-di-GMP levels, yet less is known regarding signal transmission and the targets of c-di-GMP. FimX, a protein from Pseudomonas aeruginosa that governs twitching motility, belongs to a large subfamily containing both GGDEF and EAL domains. Biochemical and structural analyses reveals its function as a high-affinity receptor for c-di-GMP. A model for full-length FimX was generated combining solution scattering data and crystal structures of the degenerate GGDEF and EAL domains. Although FimX forms a dimer in solution via the N-terminal domains, a crystallographic EAL domain dimer suggests modes for the regulation of FimX by c-di-GMP binding. The results provide the structural basis for c-di-GMP sensing via degenerate phosphodiesterases.
authors.affiliation: Department of Molecular Medicine, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA.
authors.forename: Marcos V A S
authors.initials: MV
authors.lastname: Navarro
authors.forename: Nabanita
authors.initials: N
authors.lastname: De
authors.forename: Narae
authors.initials: N
authors.lastname: Bae
authors.forename: Qi
authors.initials: Q
authors.lastname: Wang
authors.forename: Holger
authors.initials: H
authors.lastname: Sondermann
mesh_terms: D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D001665:Binding Sites; D002384:Catalysis; D003460:Crystallization; D018360:Crystallography, X-Ray; D006152:Cyclic GMP / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism; D057927:Hydrophobic and Hydrophilic Interactions; D008954:Models, Biological; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011485:Protein Binding; D011487:Protein Conformation; D017510:Protein Folding; D055503:Protein Multimerization; D017434:Protein Structure, Tertiary; D011550:Pseudomonas aeruginosa / Q000235:genetics / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction
chemical_list: D001426:Bacterial Proteins; D011956:Receptors, Cell Surface; C062025:bis(3',5')-cyclic diguanylic acid; D006152:Cyclic GMP
references.citation: Nat Struct Biol. 2003 Mar;10(3):219-25
references.pmid: 12567183
references.citation: Mol Microbiol. 2006 May;60(4):1026-43
references.pmid: 16677312
references.citation: Biophys J. 1999 Jun;76(6):2879-86
references.pmid: 10354416
references.citation: Nature. 1987 Jan 15-21;325(6101):279-81
references.pmid: 18990795
references.citation: Mol Microbiol. 2006 May;60(3):602-16
references.pmid: 16629664
references.citation: Proc Natl Acad Sci U S A. 2004 Dec 7;101(49):17084-9
references.pmid: 15569936
references.citation: Acta Crystallogr D Biol Crystallogr. 2002 Nov;58(Pt 11):1948-54
references.pmid: 12393927
references.citation: Nat Rev Microbiol. 2009 Apr;7(4):263-73
references.pmid: 19287449
references.citation: J Appl Crystallogr. 2009 Apr 1;42(Pt 2):342-346
references.pmid: 27630371
references.citation: J Biol Chem. 2006 Oct 20;281(42):32015-24
references.pmid: 16923812
references.citation: Mol Microbiol. 2005 Aug;57(3):629-39
references.pmid: 16045609
references.citation: J Bacteriol. 2009 Aug;191(15):4722-31
references.pmid: 19376848
references.citation: Curr Opin Biotechnol. 2001 Aug;12(4):376-81
references.pmid: 11551466
references.citation: Genes Dev. 2009 Jan 1;23(1):93-104
references.pmid: 19136627
references.citation: Proc Natl Acad Sci U S A. 2009 Mar 3;106(9):3461-6
references.pmid: 19218451
references.citation: Bioinformatics. 2006 Jan 1;22(1):3-6
references.pmid: 16249258
references.citation: Microbiology (Reading). 2004 Aug;150(Pt 8):2497-2502
references.pmid: 15289546
references.citation: Genes Dev. 2004 Mar 15;18(6):715-27
references.pmid: 15075296
references.citation: PLoS Biol. 2008 Mar 25;6(3):e67
references.pmid: 18366254
references.citation: Structure. 2007 Aug;15(8):915-27
references.pmid: 17697997
references.citation: J Biol Chem. 2006 Oct 13;281(41):30310-4
references.pmid: 16920715
references.citation: Proc Natl Acad Sci U S A. 1998 Dec 22;95(26):15177-82
references.pmid: 9860942
references.citation: Nature. 1975 Jun 19;255(5510):609-14
references.pmid: 1134550
references.citation: J Bacteriol. 2008 Nov;190(22):7392-405
references.pmid: 18790873
references.citation: Mol Microbiol. 2004 Aug;53(4):1123-34
references.pmid: 15306016
references.citation: Mol Microbiol. 2008 Jul;69(2):376-89
references.pmid: 18485075
references.citation: J Bacteriol. 2008 May;190(10):3622-31
references.pmid: 18344366
references.citation: Proc Natl Acad Sci U S A. 2005 Oct 4;102(40):14422-7
references.pmid: 16186483
references.citation: FEMS Microbiol Lett. 2001 Sep 11;203(1):11-21
references.pmid: 11557134
references.citation: J Mol Biol. 1999 Aug 6;291(1):149-62
references.pmid: 10438612
references.citation: J Bacteriol. 2003 Dec;185(24):7068-76
references.pmid: 14645265
references.citation: J Bacteriol. 2005 Jul;187(14):4774-81
references.pmid: 15995192
references.citation: Acta Crystallogr D Biol Crystallogr. 1996 Jul 1;52(Pt 4):842-57
references.pmid: 15299650
references.citation: J Mol Biol. 2007 Sep 21;372(3):774-97
references.pmid: 17681537
references.citation: J Biol Chem. 2005 Sep 30;280(39):33324-30
references.pmid: 16081414
references.citation: J Mol Biol. 2000 May 26;299(1):199-212
references.pmid: 10860732
references.citation: J Biol Chem. 2005 Sep 2;280(35):30829-37
references.pmid: 15994307
references.citation: Anal Biochem. 2009 Mar 1;386(1):53-8
references.pmid: 19135022
references.citation: Acta Crystallogr D Biol Crystallogr. 2004 Dec;60(Pt 12 Pt 1):2126-32
references.pmid: 15572765
references.citation: Biophys J. 2001 Jun;80(6):2946-53
references.pmid: 11371467
references.citation: Microbiology (Reading). 2009 Apr;155(Pt 4):1318-1331
references.pmid: 19332833
references.citation: J Mol Biol. 1993 Jun 20;231(4):1049-67
references.pmid: 8515464
references.citation: J Bacteriol. 2005 Mar;187(5):1792-8
references.pmid: 15716451
references.citation: Science. 2008 Jul 18;321(5887):411-3
references.pmid: 18635805
references.citation: Genes Dev. 2009 Feb 15;23(4):522-34
references.pmid: 19240136
references.citation: FEBS Lett. 1997 Oct 20;416(2):207-11
references.pmid: 9369216
references.citation: Mol Microbiol. 2007 Sep;65(6):1474-84
references.pmid: 17824927
references.citation: J Biol Chem. 2009 May 8;284(19):13174-84
references.pmid: 19244251
references.citation: J Bacteriol. 1998 Sep;180(17):4416-25
references.pmid: 9721278
references.citation: Proc Natl Acad Sci U S A. 2006 Feb 21;103(8):2839-44
references.pmid: 16477007