Use of Functional Polymorphisms To Elucidate the Peptide Binding Site of TAP Complexes

Overview

Journal J Immunol

Specialty Allergy & Immunology

Date 2015 Sep 2

PMID 26324772

Citations 10

Authors

Jie Geng

Irina D Pogozheva

Henry I Mosberg

Malini Raghavan

Affiliations

Soon will be listed here.

Abstract

TAP1/TAP2 complexes translocate peptides from the cytosol to the endoplasmic reticulum lumen to enable immune surveillance by CD8(+) T cells. Peptide transport is preceded by peptide binding to a cytosol-accessible surface of TAP1/TAP2 complexes, but the location of the TAP peptide-binding pocket remains unknown. Guided by the known contributions of polymorphic TAP variants to peptide selection, we combined homology modeling of TAP with experimental measurements to identify several TAP residues that interact with peptides. Models for peptide-TAP complexes were generated, which indicate bent conformation for peptides. The peptide binding site of TAP is located at the hydrophobic boundary of the cytosolic membrane leaflet, with striking parallels to the glutathione binding site of NaAtm1, a transporter that functions in bacterial heavy metal detoxification. These studies illustrate the conservation of the ligand recognition modes of bacterial and mammalians transporters involved in peptide-guided cellular surveillance.

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