The Structure of the Haemophilus influenzae HMW1 Pro-piece Reveals a Structural Domain Essential for Bacterial Two-partner Secretion

• Published in: The Journal of biological chemistry 2007-10, Vol.282 (42), p.31076-31084
• Main Authors: Yeo, Hye-Jeong, Yokoyama, Takeshi, Walkiewicz, Katarzyna, Kim, Youngchang, Grass, Susan, Geme, Joseph W. St
• Format: Article
• Language: English
• Subjects: Adhesins, Bacterial - chemistry; Adhesins, Bacterial - metabolism; Bacteria; Bacterial Outer Membrane Proteins - chemistry; Bacterial Outer Membrane Proteins - metabolism; Bordetella pertussis; Bordetella pertussis - chemistry; Bordetella pertussis - metabolism; Crystallography, X-Ray; Haemophilus influenzae; Haemophilus influenzae - chemistry; Haemophilus influenzae - metabolism; Protein Folding; Protein Structure, Secondary; Protein Structure, Tertiary - physiology; Structural Homology, Protein; Structure-Activity Relationship; Virulence Factors, Bordetella - chemistry; Virulence Factors, Bordetella - metabolism
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M705750200

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 1.92Å 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 β-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.