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. Author manuscript; available in PMC: 2019 Jan 5.
Published in final edited form as: Science. 2017 Oct 12;358(6366):1064–1068. doi: 10.1126/science.aao5154

Fig. 4. Importance of β2m-TAPBPR contacts and mechanism of peptide editing as viewed through the structure of the TAPBPR-MHC I complex.

Fig. 4.

(A to C) Close-up view of contact residues between hβ2m and TAPBPR: (A) β2m I7 to TAPBPR L334; (B) β2m D59 to TAPBPR K211; and (C) β2m I92/K94 to TAPBPR S330/F331. (D to F) Summary of binding of Dd73C-5mer complexes assembled with the indicated mutant hβ2m chains. (G to I) Summary of binding parameters as compared with those of the wild type (WT) (mean ± SD). Asterisks indicate the degree of statistical significance of means of multiple determinations: ****P< 0.001; ***P< 0.006; **P< 0.03 (one-way ANOVA). ns, not significant. (J) Model for TAPBPR function in peptide presentation. (1) Various peptides, ranging from low affinity (LA) to high affinity (HA), are provided to the ER after cytoplasmic proteolysis and TAP-mediated transport. (2) TAPBPR binds to MHC I, bearing a low-affinity peptide (MHC I/LA) or a peptide of suboptimal length, and catalyzes peptide dissociation. (3) TAPBPR binding remodels the peptide groove, causing release of the low-affinity peptide and stabilization of PF MHC I (TAPBPR-MHC I—PR). (4) Upon binding a high-affinity peptide, MHC I—PR changes conformation to MHC I—HA (high affinity), dissociates from TAPBPR (fig. S2), and is transported to the cell surface. This model addresses only the effects of interactions of TAPBPR with MHC I. Further experiments are needed to structurally clarify the recently described recycling pathway that employs UDP-glucose: glycoprotein glucosyltransferase 1 (UGT1) (30)