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Receptor‐Mediated ER Export of Human MHC Class I Molecules Is Regulated by the C‐Terminal Single Amino Acid
Author(s) -
Cho Sunglim,
Ryoo Jeongmin,
Jun Youngsoo,
Ahn Kwangseog
Publication year - 2011
Publication title -
traffic
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.677
H-Index - 130
eISSN - 1600-0854
pISSN - 1398-9219
DOI - 10.1111/j.1600-0854.2010.01132.x
Subject(s) - biology , major histocompatibility complex , endoplasmic reticulum , microbiology and biotechnology , transporter associated with antigen processing , mhc class i , mhc restriction , er retention , golgi apparatus , amino acid , biochemistry , antigen , genetics , mutant , gene
Major histocompatibility complex class I (MHC‐I) molecules bind antigens in the endoplasmic reticulum (ER) and deliver them to the cell surface for immune surveillance of viruses and tumors. Whereas key steps of MHC‐I assembly and its acquisition of peptides in the ER are relatively well defined, little is known about how MHC‐I molecules leave the ER for cell surface expression. Here, we show that ER export of human classical MHC‐I molecules (HLA‐A/‐B/‐C) is regulated by their C‐terminal single amino acid, valine or alanine. These amino acids, conserved in nearly all known human MHC‐I alleles, serve as the ER export signal by binding to the Sec23/24 complex, a structural component of coat protein complex II (COPII) vesicles that mediate ER‐to‐Golgi trafficking. Together, our results strongly suggest that ER export of human classical MHC‐I molecules can occur via a receptor‐mediated process dictated by a highly conserved ER export signal.