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Crystal structures of two rat mhc class ia (rt1-a) molecules that are associated differentially with peptide transporter alleles tap-a and tap-b

Academic Article
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Overview

authors

  • Rudolph, M. G.
  • Stevens, J.
  • Speir, J. A.
  • Trowsdale, J.
  • Butcher, G. W.
  • Joly, E.
  • Wilson, Ian

publication date

  • December 2002

journal

  • Journal of Molecular Biology  Journal

abstract

  • 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.

subject areas

  • ATP-Binding Cassette Transporters
  • Alleles
  • Amino Acid Sequence
  • Animals
  • Binding Sites
  • Crystallography, X-Ray
  • Histocompatibility Antigens Class I
  • Hydrogen Bonding
  • Killer Cells, Natural
  • Models, Molecular
  • Molecular Sequence Data
  • Peptides
  • Protein Binding
  • Protein Conformation
  • Rats
  • Substrate Specificity
  • Thermodynamics
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Research

keywords

  • MHC
  • NK-receptor
  • RT1-A(a)
  • RTI-Alc
  • TAP
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Identity

International Standard Serial Number (ISSN)

  • 0022-2836

Digital Object Identifier (DOI)

  • 10.1016/s0022-2836(02)01095-1

PubMed ID

  • 12470953
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Additional Document Info

start page

  • 975

end page

  • 990

volume

  • 324

issue

  • 5

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