9C2I

Inward-facing, ligand-free Multidrug Resistance-associated protein 2 (MRP2)

9C2I の概要

• エントリーDOI: 10.2210/pdb9c2i/pdb
• 関連するPDBエントリー: 9BR2 9BUK 9C12
• EMDBエントリー: 45159
• 分子名称: ATP-binding cassette sub-family C member 2, UNKNOWN LIGAND, CHOLESTEROL (3 entities in total)
• 機能のキーワード: abc transporter, multidrug resistance, regulatory domain, autoinhibition, transport protein
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 182646.77

構造登録者

Koide, E.,Chen, J. (登録日: 2024-05-31, 公開日: 2024-12-18, 最終更新日: 2025-02-12)

主引用文献

Koide, E.,Pietz, H.L.,Beltran, J.,Chen, J.
Structural basis for the transport and regulation mechanism of the multidrug resistance-associated protein 2.
Nat Commun, 16:484-484, 2025

PubMed Abstract: Multidrug resistance-associated protein 2 (MRP2) is an ATP-powered exporter important for maintaining liver homeostasis and a potential contributor to chemotherapeutic resistance. Using cryogenic electron microscopy (cryo-EM), we determine the structures of human MRP2 in three conformational states: an autoinhibited state, a substrate-bound pre-translocation state, and an ATP-bound post-translocation state. In the autoinhibited state, the cytosolic regulatory (R) domain plugs into the transmembrane substrate-binding site and extends into the cytosol to form a composite ATP-binding site at the surface of nucleotide-binding domain 2. Substrate displaces the R domain, permitting conformational changes necessary for transport. These observations suggest that the R domain functions as a selectivity gauge, where only at sufficiently high concentrations can the substrate effectively initiate transport. Comparative structural analyzes of MRP2 bound to various substrates, as determined in this study and others, reveal how MRP2 recognizes a diverse array of compounds, supporting its role in multidrug resistance.

PubMed: 39779684
DOI: 10.1038/s41467-024-55810-w

実験手法

ELECTRON MICROSCOPY (3.62 Å)