The crystal structure of Helicobacter cysteine-rich protein C at 2.0 A resolution: similar peptide-binding sites in TPR and SEL1-like repeat proteins.
Helicobacter pylori is a Gram-negative human pathogen that infects the gastric mucosa and causes an inflammatory process leading to gastritis, ulceration and cancer. Bacterial cell-surface and secreted proteins often play an important role in pathogen-host interactions and are thought to be selective mediators for the pathology of the infection. The Helicobacter cysteine-rich proteins (Hcp) represent a large family of secreted proteins that seem to be specific for microorganisms from the epsilon-subfamily of proteobacteria. Although significantly elevated levels of anti-Hcp antibodies were observed in many patients infected with H.pylori, details on the biological functions of Hcp proteins are sparse. Hcps belong to a large family of Sel1-like multi-repeat proteins. The crystal structure of HcpC was refined at 2.0 A resolution and revealed a super-helical topology composed of seven disulfide bridged alpha/alpha-repeats, an N-terminal capping helix and an extended C-terminal coil consisting of alternating hydrophobic and hydrophilic residues. In the crystal packing, the C-terminal coil interacts with the concave surface of a symmetry-related HcpC super-helix. A hydrophobic pocket and a cluster of negatively charged residues recognize the side-chains of Val290 and Lys287 from the C-terminal coil, respectively. The peptide nitrogen atom of His291 forms a short hydrogen bond with the side-chain of Asn66. The interactions seen in this crystal contact are strikingly similar to the peptide-binding modes of the Hsp70/Hsp90 organizing protein and the PEX5 receptor. The conservation of the peptide-binding mode suggests that HcpC might recognize its binding partner in a similar way.
Lüthy
Lucas
L
Biochemisches Institut, Universität Zürich, Winterthurer Strasse 190, 8057 Zurich, Switzerland.
Grütter
Markus G
MG
Mittl
Peer R E
PR
D000595:Amino Acid Sequence; D001665:Binding Sites; D003001:Cloning, Molecular; D017124:Conserved Sequence; D018360:Crystallography, X-Ray; D003545:Cysteine / Q000032:analysis*; D004220:Disulfides / Q000737:chemistry; D018840:HSP70 Heat-Shock Proteins / Q000737:chemistry; D016480:Helicobacter pylori / Q000737:chemistry*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010455:Peptides; D011485:Protein Binding; D011486:Protein C / Q000737:chemistry* / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism; D011489:Protein Denaturation; D017510:Protein Folding; D017433:Protein Structure, Secondary; D011994:Recombinant Proteins / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D013059:Spectrum Analysis, Raman; D013696:Temperature; D013816:Thermodynamics; D014867:Water / Q000737:chemistry
D004220:Disulfides; D018840:HSP70 Heat-Shock Proteins; D010455:Peptides; D011486:Protein C; D011994:Recombinant Proteins; D014867:Water; D003545:Cysteine