Loss of a glycine in the alpha2 domain affects MHC peptide binding but not chaperone binding.
Prior to the binding of peptide in the endoplasmic reticulum (ER), the major histocompatibility complex (MHC) class I heavy chain associates with an assembly complex that includes the transporter associated with antigen processing (TAP). The proximity of a part of the MHC class I alpha2 domain alpha-helix to areas previously shown to influence assembly complex binding suggests that this region might also be involved in chaperone association. Position 151, found in this part of the alpha2 domain alpha-helix, has a side chain that points up, away from direct contact with peptide, and is occupied by a glycine in all murine MHC class I heavy chains. We found that substitution of this glycine in H-2L(d) with a histidine substantially increased the proportion of peptide-free forms, although TAP binding was not abrogated. Thus, interaction of the heavy chain with peptides, but not with the assembly complex, is influenced by this glycine.
Turnquist
H R
HR
Eppley Institute for Research in Cancer and Allied Diseases, Department of Pathology and Microbiology, University of Nebraska Medical Center, 986805 Nebraska Medical Center, Omaha, Nebraska 68198-6805, USA.
Vargas
S E
SE
Solheim
J C
JC
D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D018528:ATP-Binding Cassette Transporters / Q000378:metabolism; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000818:Animals; D017951:Antigen Presentation; D001665:Binding Sites; D002460:Cell Line; D005998:Glycine / Q000737:chemistry; D006183:H-2 Antigens / Q000737:chemistry* / Q000378:metabolism*; D064532:Histocompatibility Antigen H-2D; D046911:Macromolecular Substances; D051379:Mice; D008958:Models, Molecular; D018832:Molecular Chaperones / Q000378:metabolism; D016297:Mutagenesis, Site-Directed; D009842:Oligopeptides / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary
D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D018528:ATP-Binding Cassette Transporters; D006183:H-2 Antigens; D064532:Histocompatibility Antigen H-2D; D046911:Macromolecular Substances; D018832:Molecular Chaperones; D009842:Oligopeptides; C073119:TAP1 protein, human; C486171:Tap1 protein, mouse; D005998:Glycine