title: An IgG-like domain in the minor pilin GBS52 of Streptococcus agalactiae mediates lung epithelial cell adhesion.
abstract: Streptococcus agalactiae is the leading cause of neonatal pneumonia, sepsis, and meningitis. The pathogen assembles heterotrimeric pilus structures on its surface; however, their function in pathogenesis is poorly understood. We report here the crystal structure of the pilin GBS52, which reveals two IgG-like fold domains, N1 and N2. Each domain is comprised of seven antiparallel beta strands, an arrangement similar to the fold observed in the Staphylococcus aureus adhesin Cna. Consistent with its role as an adhesin, deletion of gbs52 gene significantly reduces bacterial adherence to pulmonary epithelial cells. Moreover, latex beads linked to the GBS52 protein adhere to pulmonary but not to many other epithelial cells; binding to the former is specifically inhibited by antibodies against GBS52. Nonetheless, substantial binding is only observed with N2 domain-conjugated beads. This study presents the structure of a Gram-positive pilin that utilizes a distinct IgG fold variant to mediate pathogen adherence to a specific tissue.
authors: School of Optometry and Center for Biophysical Sciences and Engineering, University of Alabama at Birmingham, AL 35294, USA.
authors: Vengadesan
authors: V
authors: Krishnan
authors: Andrew H
authors: AH
authors: Gaspar
authors: Naiqing
authors: N
authors: Ye
authors: Anjali
authors: A
authors: Mandlik
authors: Hung
authors: H
authors: Ton-That
authors: Sthanam V L
authors: SV
authors: Narayana
mesh_terms: D001422:Bacterial Adhesion; D002460:Cell Line; D018360:Crystallography, X-Ray; D004847:Epithelial Cells / Q000382:microbiology*; D036781:Fimbriae Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D017353:Gene Deletion; D005798:Genes, Bacterial; D006801:Humans; D007074:Immunoglobulin G / Q000737:chemistry; D008168:Lung / Q000166:cytology / Q000382:microbiology; D008954:Models, Biological; D008958:Models, Molecular; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism; D013292:Streptococcus agalactiae / Q000378:metabolism* / Q000472:pathogenicity* / Q000502:physiology
chemical_list: D007074:Immunoglobulin G; D011994:Recombinant Proteins; D036781:Fimbriae Proteins
references: EMBO J. 1999 Nov 1;18(21):5817-26
references: 10545093
references: Mol Microbiol. 1995 May;16(3):575-86
references: 7565116
references: Microbiol Mol Biol Rev. 2006 Mar;70(1):192-221
references: 16524923
references: Mol Microbiol. 2004 Jul;53(1):251-61
references: 15225319
references: Acta Crystallogr D Biol Crystallogr. 1999 Apr;55(Pt 4):849-61
references: 10089316
references: Microbiol Immunol. 2005;49(9):875-84
references: 16172544
references: Nature. 1989 Apr 20;338(6217):652-5
references: 2649795
references: EMBO J. 2000 Jun 15;19(12):2803-12
references: 10856226
references: Cell. 2006 Feb 24;124(4):715-27
references: 16497583
references: Nucleic Acids Res. 2001 Jan 1;29(1):55-7
references: 11125048
references: J Bacteriol. 2003 Nov;185(22):6592-9
references: 14594832
references: Mol Microbiol. 2000 Feb;35(4):896-910
references: 10692166
references: Trends Microbiol. 2004 May;12(5):228-34
references: 15120142
references: Appl Environ Microbiol. 1997 Sep;63(9):3539-47
references: 9293004
references: EMBO J. 2002 Dec 16;21(24):6660-72
references: 12485987
references: Annu Rev Microbiol. 1994;48:585-617
references: 7826020
references: Mol Microbiol. 2006 Oct;62(2):320-30
references: 16978260
references: Proc Natl Acad Sci U S A. 2002 Sep 17;99(19):12391-6
references: 12200547
references: Acta Crystallogr D Biol Crystallogr. 1998 Sep 1;54(Pt 5):905-21
references: 9757107
references: Mol Microbiol. 2007 Apr;64(1):111-24
references: 17376076
references: Proc Natl Acad Sci U S A. 2006 Feb 21;103(8):2857-62
references: 16481624
references: J Mol Biol. 2004 Jan 16;335(3):787-97
references: 14687574
references: Mol Microbiol. 2006 Jul;61(1):126-41
references: 16824100
references: Proc Natl Acad Sci U S A. 2005 Oct 25;102(43):15641-6
references: 16223875
references: J Bacteriol. 2006 Sep;188(17):6318-25
references: 16923899
references: Nat Struct Biol. 1997 Oct;4(10):833-8
references: 9334749
references: Cell. 2003 Oct 17;115(2):217-28
references: 14567919
references: J Bacteriol. 2007 Apr;189(8):3156-65
references: 17277070
references: Mol Microbiol. 1990 Sep;4(9):1603-5
references: 2287281
references: J Bacteriol. 2006 Feb;188(4):1526-33
references: 16452436
references: J Clin Invest. 2006 Oct;116(10):2799-807
references: 17016560
references: Acta Crystallogr D Biol Crystallogr. 1999 Oct;55(Pt 10):1718-25
references: 10531521
references: Acta Crystallogr D Biol Crystallogr. 1994 Sep 1;50(Pt 5):760-3
references: 15299374
references: Biochemistry. 1998 Nov 3;37(44):15423-33
references: 9799504
references: Structure. 2000 Jan 15;8(1):67-78
references: 10673425
references: Mol Cell. 2003 May;11(5):1139-50
references: 12769840
references: Acta Crystallogr D Biol Crystallogr. 2004 Dec;60(Pt 12 Pt 1):2126-32
references: 15572765
references: EMBO J. 2005 Dec 21;24(24):4224-36
references: 16362049
references: Cell. 2001 Jun 15;105(6):733-43
references: 11440716
references: J Biol Chem. 2001 Jan 5;276(1):139-46
references: 11027683
references: Nat Rev Microbiol. 2006 Jul;4(7):509-19
references: 16778837
references: Mol Microbiol. 2006 Jun;60(6):1401-13
references: 16796677
references: Microbes Infect. 2000 Nov;2(14):1733-42
references: 11137046
references: Mol Microbiol. 2004 Oct;54(1):23-31
references: 15458402
references: Mol Microbiol. 2003 Nov;50(4):1429-38
references: 14622427