title: Structural requirements for the peptide-induced conformational change of free major histocompatibility complex class I heavy chains.
abstract: In an attempt to define the structural features of peptides which are important for inducing the folding of free class I heavy chains in the absence of beta 2-microglobulin, and to determine whether they are the same as those required to form stable major histocompatibility complex (MHC): peptide adducts, we have used a panel of peptides related to the Db-binding nonamer ASNENMDAM (influenza nucleoprotein residues 366-374) with altered primary structures, and a number of other peptides which have the Db-binding "motif". In this way, we have shown that in addition to the "anchor" residues which define this motif, the alpha amino and carboxyl groups at the N and C termini also play a major role in both inducing the conformational change in free heavy chain (HC) and formation of a stable Db:peptide complex. We also show that the importance of the key residues is affected by the primary sequence "context" in which they appear. In addition, we have extended our original finding that naturally processed epitopes induce a conformational change in free HC to the H2Kb HC, and show that the effect does not require the presence of the class I alpha 3 domain.
authors.affiliation: Institute for Molecular Medicine, John Radcliffe Hospital, Oxford, GB.
authors.forename: T
authors.initials: T
authors.lastname: Elliott
authors.forename: J
authors.initials: J
authors.lastname: Elvin
authors.forename: V
authors.initials: V
authors.lastname: Cerundolo
authors.forename: H
authors.initials: H
authors.lastname: Allen
authors.forename: A
authors.initials: A
authors.lastname: Townsend
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D006183:H-2 Antigens / Q000737:chemistry* / Q000378:metabolism; D064532:Histocompatibility Antigen H-2D; D051379:Mice; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000494:pharmacology*; D011487:Protein Conformation; D013329:Structure-Activity Relationship
chemical_list: D006183:H-2 Antigens; D064532:Histocompatibility Antigen H-2D; D010446:Peptide Fragments