Document Detail


Crystal structure of an Fab fragment in complex with a meningococcal serosubtype antigen and a protein G domain.
MedLine Citation:
PMID:  10512717     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Many pathogens present highly variable surface proteins to their host as a means of evading immune responses. The structure of a peptide antigen corresponding to the subtype P1.7 variant of the porin PorA from the human pathogen Neisseria meningitidis was determined by solution of the X-ray crystal structure of the ternary complex of the peptide (ANGGASGQVK) in complex with a Fab fragment and a domain from streptococcal protein G to 1.95 A resolution. The peptide adopted a beta-hairpin structure with a type I beta-turn between residues Gly4P and Gly7P, the conformation of the peptide being further stabilised by a pair of hydrogen bonds from the side-chain of Asn2P to main-chain atoms in Val9P. The antigen binding site within the Fab formed a distinct crevice lined by a high proportion of apolar amino acids. Recognition was supplemented by hydrogen bonds from heavy chain residues Thr50H, Asp95H, Leu97H and Tyr100H to main-chain and side-chain atoms in the peptide. Complementarity-determining region (CDR) 3 of the heavy chain was responsible for approximately 50 % of the buried surface area formed by peptide-Fab binding, with the remainder made up from CDRs 1 and 3 of the light chain and CDRs 1 and 2 of the heavy chain. Knowledge of the structures of variable surface antigens such as PorA is an essential prerequisite to a molecular understanding of antigenic variation and its implications for vaccine design.
Authors:
J P Derrick; M C Maiden; I M Feavers
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of molecular biology     Volume:  293     ISSN:  0022-2836     ISO Abbreviation:  J. Mol. Biol.     Publication Date:  1999 Oct 
Date Detail:
Created Date:  1999-11-22     Completed Date:  1999-11-22     Revised Date:  2011-08-01    
Medline Journal Info:
Nlm Unique ID:  2985088R     Medline TA:  J Mol Biol     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  81-91     Citation Subset:  IM    
Copyright Information:
Copyright 1999 Academic Press.
Affiliation:
Department of Biomolecular Sciences, UMIST, Manchester, M60 1QD, UK. Jeremy.Derrick@umist.ac.uk
Data Bank Information
Bank Name/Acc. No.:
PDB/1QKZ
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MeSH Terms
Descriptor/Qualifier:
Amino Acid Sequence
Animals
Antibodies, Monoclonal / chemistry*,  immunology
Antigenic Variation
Antigens, Bacterial / chemistry
Binding Sites
Crystallography, X-Ray
Hydrogen Bonding
Immunoglobulin Fab Fragments / chemistry*
Immunoglobulin Heavy Chains / chemistry
Immunoglobulin Light Chains / chemistry
Immunoglobulin Variable Region / chemistry
Mice
Models, Molecular
Molecular Sequence Data
Neisseria meningitidis / immunology*
Nerve Tissue Proteins / chemistry*,  immunology
Porins / chemistry*
Protein Structure, Secondary
Sequence Alignment
Grant Support
ID/Acronym/Agency:
//Wellcome Trust
Chemical
Reg. No./Substance:
0/Antibodies, Monoclonal; 0/Antigens, Bacterial; 0/G-substrate; 0/Immunoglobulin Fab Fragments; 0/Immunoglobulin Heavy Chains; 0/Immunoglobulin Light Chains; 0/Immunoglobulin Variable Region; 0/MOPC21 monoclonal antibody; 0/Nerve Tissue Proteins; 0/Porins; 0/porin protein, Neisseria

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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