Document Detail


Analysis of two acidic P6 pocket residues in the pH dependency of peptide binding by I-E(k).
MedLine Citation:
PMID:  12044780     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Peptide binding to major histocompatibility complex (MHC) class II molecules is optimal at mildly acidic pH. X-ray crystal structures solved for the murine class II molecule I-E(k) revealed an interesting localization of negatively charged residues within the P6 pocket, which may have implications in the pH dependency of peptide binding. Protonation of these critical residues, under acidic conditions, has been proposed to be important for the formation of stable class II-peptide complexes. In this study, we address a possible role for these charged residues in the pH dependency of peptide binding. An I-E(k) mutant was generated in which two acidic residues of the P6 pocket were substituted with uncharged residues. This class II mutant was expressed, purified, and tested for its ability to bind peptides. The mutant I-E(k) was observed to load peptides optimally at mildly acidic pH. Peptide binding to the mutant was enhanced in the presence of DM, and optimal DM-enhanced binding occurred in the acidic pH range. These findings indicate that structural changes other than protonation of acidic residues in pocket 6 must play a dominant role in pH-regulated peptide binding to I-E(k).
Authors:
Chinh T Dao; Dominique A Weber; Peter E Jensen
Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Molecular immunology     Volume:  38     ISSN:  0161-5890     ISO Abbreviation:  Mol. Immunol.     Publication Date:  2002 Jun 
Date Detail:
Created Date:  2002-06-04     Completed Date:  2003-07-22     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  7905289     Medline TA:  Mol Immunol     Country:  England    
Other Details:
Languages:  eng     Pagination:  1139-49     Citation Subset:  IM    
Affiliation:
Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Aspartic Acid / metabolism
Glutamic Acid / metabolism
HLA-D Antigens / metabolism
Histocompatibility Antigens Class II / genetics,  metabolism*
Humans
Hydrogen-Ion Concentration
Mice
Mutation
Peptides / metabolism*
Protein Conformation
Grant Support
ID/Acronym/Agency:
AI30554/AI/NIAID NIH HHS; AI33614/AI/NIAID NIH HHS
Chemical
Reg. No./Substance:
0/HLA-D Antigens; 0/HLA-DMB; 0/Histocompatibility Antigens Class II; 0/I-E-antigen; 0/Peptides; 56-84-8/Aspartic Acid; 56-86-0/Glutamic Acid

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