title: Structure of the Chlamydia trachomatis immunodominant antigen Pgp3.
abstract: Chlamydia trachomatis infection is the most common sexually transmitted bacterial disease. Left untreated, it can lead to ectopic pregnancy, pelvic inflammatory disease, and infertility. Here we present the structure of the secreted C. trachomatis protein Pgp3, an immunodominant antigen and putative virulence factor. The ∼84-kDa Pgp3 homotrimer, encoded on a cryptic plasmid, consists of globular N- and C-terminal assemblies connected by a triple-helical coiled-coil. The C-terminal domains possess folds similar to members of the TNF family of cytokines. The closest Pgp3 C-terminal domain structural homologs include a lectin from Burkholderia cenocepacia, the C1q component of complement, and a portion of the Bacillus anthracis spore surface protein BclA, all of which play roles in bioadhesion. The N-terminal domain consists of a concatenation of structural motifs typically found in trimeric viral proteins. The central parallel triple-helical coiled-coil contains an unusual alternating pattern of apolar and polar residue pairs that generate a rare right-handed superhelical twist. The unique architecture of Pgp3 provides the basis for understanding its role in chlamydial pathogenesis and serves as the platform for its optimization as a potential vaccine antigen candidate.
authors.affiliation: Department of Biochemistry, University of Texas Health Science Center, San Antonio, Texas 78229, USA.
authors.forename: Ahmad
authors.initials: A
authors.lastname: Galaleldeen
authors.forename: Alexander B
authors.initials: AB
authors.lastname: Taylor
authors.forename: Ding
authors.initials: D
authors.lastname: Chen
authors.forename: Jonathan P
authors.initials: JP
authors.lastname: Schuermann
authors.forename: Stephen P
authors.initials: SP
authors.lastname: Holloway
authors.forename: Shuping
authors.initials: S
authors.lastname: Hou
authors.forename: Siqi
authors.initials: S
authors.lastname: Gong
authors.forename: Guangming
authors.initials: G
authors.lastname: Zhong
authors.forename: P John
authors.initials: PJ
authors.lastname: Hart
mesh_terms: D000942:Antigens, Bacterial / Q000737:chemistry* / Q000235:genetics; D001426:Bacterial Proteins / Q000737:chemistry* / Q000235:genetics; D002690:Chlamydia Infections / Q000382:microbiology; D002692:Chlamydia trachomatis / Q000235:genetics / Q000276:immunology; D018360:Crystallography, X-Ray; D005260:Female; D006801:Humans; D016056:Immunodominant Epitopes / Q000737:chemistry* / Q000235:genetics; D008958:Models, Molecular; D011247:Pregnancy; D011271:Pregnancy, Ectopic / Q000382:microbiology; D017510:Protein Folding; D055503:Protein Multimerization; D020836:Protein Structure, Quaternary; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000737:chemistry
chemical_list: D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D016056:Immunodominant Epitopes; D011994:Recombinant Proteins; C082169:pgp3 protein, Chlamydia
keywords: Bacterial Pathogenesis; Beta-Helix; Beta-Propeller; Chlamydia; Helical Coiled-coil; Immunology; Pgp3; Sexually Transmitted Disease; Tumor Necrosis Factor (TNF); X-ray Crystallography