Linked Life Data

7664799

Source:http://linkedlifedata.com/resource/pubmed/id/7664799

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
8
pubmed:dateCreated
1995-10-10
pubmed:abstractText
The results in this study address three aspects of peptide binding to the disease-associated antigen HLA-B27 and its modulation by polymorphism: the contribution of major anchor residues 2 and 9, the role of pocket B polymorphism in modulating peptide specificity, and the binding properties of B*2703, a subtype not found to be associated with spondyloarthropathy. Synthetic analogs of peptides naturally presented by B*2705 were used to demonstrate that residue 2 is essential, since Ala2 analogs bound marginally to B*2705, but the specificity of B*2705 for Arg2 is not absolute, and show that the contribution of basic residue 9 to binding was significant, but less than Arg2. The effect of single mutations in the B pocket was to decrease or--with the Glu > Met-45 mutation--totally shift pocket B specificity for Arg2 towards other residues at this position. This was shown by quantitating the relative binding of Gln2 and Ala2 analogs, and by pool-sequencing of the peptides bound in vivo to these mutants. Peptides naturally presented by B*2705 apparently bound with a lower affinity to pocket A variants with altered hydrogen bonding to the peptide N terminus, including B*2703. Binding of peptide analogs with changes at positions 2 or 9 suggested that in B*2703 pocket A, interactions are weaker and pocket B interactions are stronger than in B*2705. This can be explained by the effect of the unique His59 change in B*2703 in both pockets. Thus, B*2703 is probably the HLA-B27 sub-type with the most stringent specificity for the Arg2 peptide motif.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0014-2980
pubmed:author
pubmed:issnType
Print
pubmed:volume
25
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2370-7
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1995
pubmed:articleTitle
Modulation of peptide binding by HLA-B27 polymorphism in pockets A and B, and peptide specificity of B*2703.
pubmed:affiliation
Centro de Biología Molecular, Severo Ochoa (C.S.I.C.-U.A.M.), Universidad Autónoma de Madrid, Facultad de Ciencias, Spain.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't