6RQX

High-resolution crystal structure of ERAP1 in complex with 10mer phosphinic peptide

6RQX の概要

• エントリーDOI: 10.2210/pdb6rqx/pdb
• 関連するPDBエントリー: 2YD0 3MDJ 6Q4R
• 分子名称: Endoplasmic reticulum aminopeptidase 1, SODIUM ION, TRIETHYLENE GLYCOL, ... (12 entities in total)
• 機能のキーワード: endoplasmic reticulum aminopeptidase 1, erap1, antigen presentation, hydrolase
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 112814.68

構造登録者

Giastas, P.,Stratikos, E. (登録日: 2019-05-16, 公開日: 2019-12-18, 最終更新日: 2024-11-13)

主引用文献

Giastas, P.,Mpakali, A.,Papakyriakou, A.,Lelis, A.,Kokkala, P.,Neu, M.,Rowland, P.,Liddle, J.,Georgiadis, D.,Stratikos, E.
Mechanism for antigenic peptide selection by endoplasmic reticulum aminopeptidase 1.
Proc.Natl.Acad.Sci.USA, 2019

PubMed Abstract: Endoplasmic reticulum aminopeptidase 1 (ERAP1) is an intracellular enzyme that optimizes the peptide cargo of major histocompatibility class I (MHC-I) molecules and regulates adaptive immunity. It has unusual substrate selectivity for length and sequence, resulting in poorly understood effects on the cellular immunopeptidome. To understand substrate selection by ERAP1, we solved 2 crystal structures of the enzyme with bound transition-state pseudopeptide analogs at 1.68 Å and 1.72 Å. Both peptides have their N terminus bound at the active site and extend away along a large internal cavity, interacting with shallow pockets that can influence selectivity. The longer peptide is disordered through the central region of the cavity and has its C terminus bound in an allosteric pocket of domain IV that features a carboxypeptidase-like structural motif. These structures, along with enzymatic and computational analyses, explain how ERAP1 can select peptides based on length while retaining the broad sequence-specificity necessary for its biological function.

PubMed: 31843903
DOI: 10.1073/pnas.1912070116

実験手法

X-RAY DIFFRACTION (1.68 Å)