Linked Life Data

12470953

Source:http://linkedlifedata.com/resource/pubmed/id/12470953

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2002-12-9
pubmed:databankReference
pubmed:abstractText
Antigenic peptides are loaded onto class I MHC molecules in the endoplasmic reticulum (ER) by a complex consisting of the MHC class I heavy chain, beta(2)-microglobulin, calreticulin, tapasin, Erp57 (ER60) and the transporter associated with antigen processing (TAP). While most mammalian species transport these peptides into the ER via a single allele of TAP, rats have evolved different TAPs, TAP-A and TAP-B, that are present in different inbred strains. Each TAP delivers a different spectrum of peptides and is associated genetically with distinct subsets of MHC class Ia alleles, but the molecular basis for the conservation (or co-evolution) of the two transporter alleles is unknown. We have determined the crystal structures of a representative of each MHC subset, viz RT1-A(a) and RT1-A1(c), in association with high-affinity nonamer peptides. The structures reveal how the chemical properties of the two different rat MHC F-pockets match those of the corresponding C termini of the peptides, corroborating biochemical data on the rates of peptide-MHC complex assembly. An unusual sequence in RT1-A1(c) leads to a major deviation from the highly conserved beta(3)/alpha(1) loop (residues 40-59) conformation in mouse and human MHC class I structures. This loop change contributes to profound changes in the shape of the A-pocket in the peptide-binding groove and may explain the function of RT1-A1(c) as an inhibitory natural killer cell ligand.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0022-2836
pubmed:author
pubmed:issnType
Print
pubmed:day
13
pubmed:volume
324
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
975-90
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:12470953-ATP-Binding Cassette Transporters, pubmed-meshheading:12470953-Alleles, pubmed-meshheading:12470953-Amino Acid Sequence, pubmed-meshheading:12470953-Animals, pubmed-meshheading:12470953-Binding Sites, pubmed-meshheading:12470953-Crystallography, X-Ray, pubmed-meshheading:12470953-Histocompatibility Antigens Class I, pubmed-meshheading:12470953-Hydrogen Bonding, pubmed-meshheading:12470953-Killer Cells, Natural, pubmed-meshheading:12470953-Models, Molecular, pubmed-meshheading:12470953-Molecular Sequence Data, pubmed-meshheading:12470953-Peptides, pubmed-meshheading:12470953-Protein Binding, pubmed-meshheading:12470953-Protein Conformation, pubmed-meshheading:12470953-Rats, pubmed-meshheading:12470953-Substrate Specificity, pubmed-meshheading:12470953-Thermodynamics
pubmed:year
2002
pubmed:articleTitle
Crystal structures of two rat MHC class Ia (RT1-A) molecules that are associated differentially with peptide transporter alleles TAP-A and TAP-B.
pubmed:affiliation
Department of Molecular Biology and Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't