The N-terminal region of tapasin is required to stabilize the MHC class I loading complex.
Tapasin mediates the binding of MHC class I molecules to the transporter associated with antigen processing (TAP). Deletion mutants of tapasin were used to examine the effect of tapasin on interactions within the MHC class I complex. Binding to TAP is mediated by the C-terminal region of tapasin. Michaelis-Menten analysis of peptide transport shows that this interaction is sufficient to increase TAP levels without significantly affecting the intrinsic translocation rate. Weak interactions exist between MHC class I molecules and TAP in the absence of tapasin, and between free heavy chains and TAP-tapasin complexes in the absence of beta2-microglobulin. The N-terminal 50 residues of tapasin constitute the key element which converts the sum of these weak interactions into a stable complex.
Bangia
N
N
Howard Hughes Medical Institute, Section of Immunobiology, Yale University School of Medicine, New Haven, CT 06520-8011, USA.
Lehner
P J
PJ
Hughes
E A
EA
Surman
M
M
Cresswell
P
P
D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D018528:ATP-Binding Cassette Transporters / Q000378:metabolism; D017951:Antigen Presentation; D017920:Antiporters / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D001693:Biological Transport, Active; D002135:Calcium-Binding Proteins / Q000378:metabolism; D037282:Calreticulin; D002460:Cell Line; D017931:DNA Primers / Q000235:genetics; D004355:Drug Stability; D006360:Heat-Shock Proteins / Q000378:metabolism; D015395:Histocompatibility Antigens Class I / Q000378:metabolism*; D006801:Humans; D007136:Immunoglobulins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D007535:Isomerases / Q000378:metabolism; D007700:Kinetics; D046911:Macromolecular Substances; D026901:Membrane Transport Proteins; D018832:Molecular Chaperones / Q000378:metabolism; D011485:Protein Binding; D019704:Protein Disulfide-Isomerases; D012261:Ribonucleoproteins / Q000378:metabolism; D001613:beta 2-Microglobulin / Q000378:metabolism
D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D018528:ATP-Binding Cassette Transporters; D017920:Antiporters; D002135:Calcium-Binding Proteins; D037282:Calreticulin; D017931:DNA Primers; D006360:Heat-Shock Proteins; D015395:Histocompatibility Antigens Class I; D007136:Immunoglobulins; D046911:Macromolecular Substances; D026901:Membrane Transport Proteins; D018832:Molecular Chaperones; D012261:Ribonucleoproteins; C073119:TAP1 protein, human; D001613:beta 2-Microglobulin; C107762:tapasin; D007535:Isomerases; D019704:Protein Disulfide-Isomerases; C085868:PDIA3 protein, human