7DQV

Crystal structure of a CmABCB1 mutant

7DQV の概要

• エントリーDOI: 10.2210/pdb7dqv/pdb
• 分子名称: Probable ATP-dependent transporter ycf16, PHOSPHOAMINOPHOSPHONIC ACID-ADENYLATE ESTER, DECYL-BETA-D-MALTOPYRANOSIDE, ... (6 entities in total)
• 機能のキーワード: multidrug resistance abc transporter membrane protein, transport protein
• 由来する生物種: Cyanidioschyzon merolae (strain 10D) (Red alga)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 68834.52

構造登録者

Matsuoka, K.,Nakatsu, T.,Kato, H. (登録日: 2020-12-24, 公開日: 2021-03-24, 最終更新日: 2023-11-29)

主引用文献

Matsuoka, K.,Nakatsu, T.,Kato, H.
The crystal structure of the CmABCB1 G132V mutant, which favors the outward-facing state, reveals the mechanism of the pivotal joint between TM1 and TM3.
Protein Sci., 30:1064-1071, 2021

PubMed Abstract: CmABCB1 is a homologue of human P-glycoprotein, which extrudes various substrates by iterative cycles of conformational changes between the inward- and outward-facing states. Comparison of the inward- and outward-facing structures of CmABCB1 suggested that pivotal joints in the transmembrane domain regulate the tilt of transmembrane helices. Transmembrane helix 1 (TM1) forms a tight helix-helix contact with TM3 at the TM1-3 joint. Mutation of Gly132 to valine at the TM1-3 joint, G132V, caused a 10-fold increase in ATPase activity, but the mechanism underlying this change remains unclear. Here, we report a crystal structure of the outward-facing state of the CmABCB1 G132V mutant at a 2.15 Å resolution. We observed structural displacements between the outward-facing states of G132V and the previous one at the region around the TM1-3 joint, and a significant expansion at the extracellular gate. We hypothesize that steric hindrance caused by the Val substitution shifted the conformational equilibrium toward the outward-facing state, favoring the dimeric state of the nucleotide-binding domains and thereby increasing the ATPase activity of the G132V mutant.

PubMed: 33683740
DOI: 10.1002/pro.4058

実験手法

X-RAY DIFFRACTION (2.15 Å)