Linked Life Data

16229893

Source:http://linkedlifedata.com/resource/pubmed/id/16229893

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
9
pubmed:dateCreated
2006-2-28
pubmed:abstractText
Beta-2 microglobulin (beta2m) is a member of the immunoglobulin-like domain superfamily that is an essential structural subunit of the MHC class I (MHC-I) molecule. beta2m was previously identified as a susceptibility factor for the development of type 1 diabetes (T1D) in NOD mice, whereby transgenic expression of the beta2ma variant, but not the beta2mb variant, restored diabetes susceptibility to normally resistant NOD.beta2mnull mice. Here we report the crystal structures and thermodynamic stabilities of the NOD MHC-I molecule H2-Db containing these two variants. Our results reveal subtle differences in the structures of the beta2m variants, namely in minor loop shifts and in variations in the hydrogen bonding networks at the interfaces between the components of the ternary complex. We also demonstrate that the thermodynamic stabilities of the beta2m variants in isolation differ. However, the conformation of the peptide in the MHC cleft is unchanged in beta2m allelic Db complexes, as are the TCR recognition surfaces. Thus, despite modest structural differences between allelic complexes, the evidence indicates that Db peptide presentation of the representative peptide is unchanged in the context of either beta2m allelic variant. These data suggest that other mechanisms, such as differential association of MHC-I in multiprotein complexes, are likely responsible for the effect of beta2m on T1D development.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0161-5890
pubmed:author
pubmed:issnType
Print
pubmed:volume
43
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1370-8
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed:year
2006
pubmed:articleTitle
Structural analysis of H2-Db class I molecules containing two different allelic forms of the type 1 diabetes susceptibility factor beta-2 microglobulin: implications for the mechanism underlying variations in antigen presentation.
pubmed:affiliation
Department of Microbiology and Immunology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA.
pubmed:publicationType
Journal Article, In Vitro, Research Support, N.I.H., Extramural