Structure of the TAPBPR-MHC I complex defines the mechanism of peptide loading and editing

Science. 2017 Nov 24;358(6366):1060-1064. doi: 10.1126/science.aao6001. Epub 2017 Oct 12.

Abstract

Adaptive immunity is shaped by a selection of peptides presented on major histocompatibility complex class I (MHC I) molecules. The chaperones Tapasin (Tsn) and TAP-binding protein-related (TAPBPR) facilitate MHC I peptide loading and high-affinity epitope selection. Despite the pivotal role of Tsn and TAPBPR in controlling the hierarchical immune response, their catalytic mechanism remains unknown. Here, we present the x-ray structure of the TAPBPR-MHC I complex, which delineates the central step of catalysis. TAPBPR functions as peptide selector by remodeling the MHC I α2-1-helix region, stabilizing the empty binding groove, and inserting a loop into the groove that interferes with peptide binding. The complex explains how mutations in MHC I-specific chaperones cause defects in antigen processing and suggests a unifying mechanism of peptide proofreading.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biocatalysis
  • Crystallography, X-Ray
  • Histocompatibility Antigens Class I / chemistry*
  • Histocompatibility Antigens Class I / ultrastructure
  • Humans
  • Immunoglobulins / chemistry*
  • Immunoglobulins / ultrastructure
  • Membrane Proteins / chemistry*
  • Membrane Proteins / ultrastructure
  • Peptides / chemistry
  • Protein Conformation
  • beta 2-Microglobulin / chemistry*
  • beta 2-Microglobulin / ultrastructure

Substances

  • Histocompatibility Antigens Class I
  • Immunoglobulins
  • Membrane Proteins
  • Peptides
  • TAPBPL protein, human
  • beta 2-Microglobulin