7P1K

Cryo EM structure of bison NHA2 in nano disc structure

7P1K の概要

• エントリーDOI: 10.2210/pdb7p1k/pdb
• EMDBエントリー: 13163
• 分子名称: mitochondrial sodium/hydrogen exchanger 9B2, CHOLESTEROL HEMISUCCINATE, Phosphatidylinositol (3 entities in total)
• 機能のキーワード: membrane protein sodium proton transporter, transport protein
• 由来する生物種: Bison bison (American bison)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 122280.73

構造登録者

Matsuoka, R.,Fudim, R.,Jung, S.,Drew, D. (登録日: 2021-07-01, 公開日: 2022-01-26, 最終更新日: 2025-07-02)

主引用文献

Matsuoka, R.,Fudim, R.,Jung, S.,Zhang, C.,Bazzone, A.,Chatzikyriakidou, Y.,Robinson, C.V.,Nomura, N.,Iwata, S.,Landreh, M.,Orellana, L.,Beckstein, O.,Drew, D.
Structure, mechanism and lipid-mediated remodeling of the mammalian Na + /H + exchanger NHA2.
Nat.Struct.Mol.Biol., 29:108-120, 2022

PubMed Abstract: The Na/H exchanger SLC9B2, also known as NHA2, correlates with the long-sought-after Na/Li exchanger linked to the pathogenesis of diabetes mellitus and essential hypertension in humans. Despite the functional importance of NHA2, structural information and the molecular basis for its ion-exchange mechanism have been lacking. Here we report the cryo-EM structures of bison NHA2 in detergent and in nanodiscs, at 3.0 and 3.5 Å resolution, respectively. The bison NHA2 structure, together with solid-state membrane-based electrophysiology, establishes the molecular basis for electroneutral ion exchange. NHA2 consists of 14 transmembrane (TM) segments, rather than the 13 TMs previously observed in mammalian Na/H exchangers (NHEs) and related bacterial antiporters. The additional N-terminal helix in NHA2 forms a unique homodimer interface with a large intracellular gap between the protomers, which closes in the presence of phosphoinositol lipids. We propose that the additional N-terminal helix has evolved as a lipid-mediated remodeling switch for the regulation of NHA2 activity.

PubMed: 35173351
DOI: 10.1038/s41594-022-00738-2

実験手法

ELECTRON MICROSCOPY (3.64 Å)