9O9S

Structure of human MPC matrix-open

9O9S の概要

• エントリーDOI: 10.2210/pdb9o9s/pdb
• EMDBエントリー: 70261
• 分子名称: Mitochondrial pyruvate carrier 1/MBP chimera protein, Mitochondrial pyruvate carrier 2, (E)-2-cyano-3-(1-phenylindol-3-yl)prop-2-enoic acid (3 entities in total)
• 機能のキーワード: membrane protein
• 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: 84183.01

構造登録者

Qi, X.,Sun, Y.,Wang, Y. (登録日: 2025-04-18, 公開日: 2025-07-30, 最終更新日: 2026-02-11)

主引用文献

Sun, Y.,Wang, Y.,Xing, Z.,Li, D.,Wang, R.,Chen, B.,Zhou, N.,Ayala, A.,Tu, B.P.,Qi, X.
Structure of human mitochondrial pyruvate carrier MPC1 and MPC2 complex.
Nat Commun, 16:6700-6700, 2025

PubMed Abstract: The Mitochondrial Pyruvate Carrier (MPC) bridges cytosolic and mitochondrial metabolism by transporting pyruvate into mitochondria for ATP production and biosynthesis of various essential molecules. MPC functions as a heterodimer composed of MPC1 and MPC2 in most mammalian cells. Here, we present the cryogenic electron microscopy (cryo-EM) structures of the human MPC1-2 complex in the mitochondrial intermembrane space (IMS)-open state and the inhibitor-bound in the mitochondrial matrix-open state. Structural analysis shows that the transport channel of MPC is formed by the interaction of transmembrane helix (TM) 1 and TM2 of MPC1 with TM2 and TM1 of MPC2, respectively. UK5099, a potent MPC inhibitor, shares the same binding site with pyruvate at the matrix side of the transport channel, stabilizing MPC in its matrix-open conformation. Notably, a functional W82F mutation in MPC2 leads to the complex in an IMS-open conformation. Structural comparisons across different conformations, combined with yeast rescue assays, reveal the mechanisms of substrate binding and asymmetric conformational changes in MPC during pyruvate transport across the inner mitochondrial membrane (IMM) as well as the inhibitory mechanisms of MPC inhibitors.

PubMed: 40691140
DOI: 10.1038/s41467-025-61939-z

実験手法

ELECTRON MICROSCOPY (3.57 Å)