title: The structure of the Haemophilus influenzae HMW1 pro-piece reveals a structural domain essential for bacterial two-partner secretion.
abstract: In pathogenic Gram-negative bacteria, many virulence factors are secreted via the two-partner secretion pathway, which consists of an exoprotein called TpsA and a cognate outer membrane translocator called TpsB. The HMW1 and HMW2 adhesins are major virulence factors in nontypeable Haemophilus influenzae and are prototype two-partner secretion pathway exoproteins. A key step in the delivery of HMW1 and HMW2 to the bacterial surface involves targeting to the HMW1B and HMW2B outer membrane translocators by an N-terminal region called the secretion domain. Here we present the crystal structure at 1.92 A of the HMW1 pro-piece (HMW1-PP), a region that contains the HMW1 secretion domain and is cleaved and released during HMW1 secretion. Structural analysis of HMW1-PP revealed a right-handed beta-helix fold containing 12 complete parallel coils and one large extra-helical domain. Comparison of HMW1-PP and the Bordetella pertussis FHA secretion domain (Fha30) reveals limited amino acid homology but shared structural features, suggesting that diverse TpsA proteins have a common structural domain required for targeting to cognate TpsB proteins. Further comparison of HMW1-PP and Fha30 structures may provide insights into the keen specificity of TpsA-TpsB interactions.
authors: Department of Biology and Biochemistry, University of Houston, Houston, Texas 77204, USA. hyeo@uh.edu
authors: Hye-Jeong
authors: HJ
authors: Yeo
authors: Takeshi
authors: T
authors: Yokoyama
authors: Katarzyna
authors: K
authors: Walkiewicz
authors: Youngchang
authors: Y
authors: Kim
authors: Susan
authors: S
authors: Grass
authors: Joseph W St
authors: JW
authors: Geme
mesh_terms: D018829:Adhesins, Bacterial / Q000737:chemistry* / Q000378:metabolism; D001425:Bacterial Outer Membrane Proteins / Q000737:chemistry / Q000378:metabolism; D001886:Bordetella pertussis / Q000737:chemistry / Q000378:metabolism; D018360:Crystallography, X-Ray; D006193:Haemophilus influenzae / Q000737:chemistry* / Q000378:metabolism; D017510:Protein Folding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary / Q000502:physiology*; D040681:Structural Homology, Protein; D013329:Structure-Activity Relationship; D010566:Virulence Factors, Bordetella / Q000737:chemistry / Q000378:metabolism
chemical_list: D018829:Adhesins, Bacterial; D001425:Bacterial Outer Membrane Proteins; C117431:HMW1 protein, bacteria; C117432:HMW2 protein, bacteria; D010566:Virulence Factors, Bordetella; C065273:filamentous hemagglutinin adhesin, Bordetella pertussis