8VVC

Cryo-EM structure of human ABC transporter (hABCC1) with nucleotide-binding domain 2

8VVC の概要

• エントリーDOI: 10.2210/pdb8vvc/pdb
• EMDBエントリー: 43550
• 分子名称: Multidrug resistance-associated protein 1 (1 entity in total)
• 機能のキーワード: cgamp exporter, multidrug-resistant protein, abc transporter, membrane 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: 171762.95

構造登録者

Shinde, O.,Li, P. (登録日: 2024-01-30, 公開日: 2024-12-25, 最終更新日: 2025-01-29)

主引用文献

Shinde, O.,Boyer, J.A.,Cambier, S.,VanPortfliet, J.J.,Sui, X.,Yadav, G.P.,Viverette, E.G.,Borgnia, M.J.,West, A.P.,Zhang, Q.,Stetson, D.B.,Li, P.
Structures of ATP-binding cassette transporter ABCC1 reveal the molecular basis of cyclic dinucleotide cGAMP export.
Immunity, 58:59-73.e5, 2025

PubMed Abstract: Cyclic nucleotide GMP-AMP (cGAMP) plays a critical role in mediating the innate immune response through the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway. Recent studies showed that ATP-binding cassette subfamily C member 1 (ABCC1) is a cGAMP exporter. The exported cGAMP can be imported into uninfected cells to stimulate a STING-mediated innate immune response. However, the molecular basis of cGAMP export mediated by ABCC1 remains unclear. Here, we report the cryoelectron microscopy (cryo-EM) structures of human ABCC1 in a ligand-free state and a cGAMP-bound state. These structures reveal that ABCC1 forms a homodimer via its N-terminal transmembrane domain. The ligand-bound structure shows that cGAMP is recognized by a positively charged pocket. Mutagenesis and functional studies confirmed the roles of the ligand-binding pocket in cGAMP recognition and export. This study provides insights into the structure and function of ABCC1 as a cGAMP exporter and lays a foundation for future research targeting ABCC1 in infection and anti-cancer immunity.

PubMed: 39765229
DOI: 10.1016/j.immuni.2024.12.002

実験手法

ELECTRON MICROSCOPY (4.32 Å)