Structure, mechanism and lipid-mediated remodeling of the mammalian Na+/H+ exchanger NHA2

DOI PDF Web Site 研究データあり 参考文献87件

この論文をさがす

説明

<jats:title>Abstract</jats:title><jats:p>The Na<jats:sup>+</jats:sup>/H<jats:sup>+</jats:sup> exchanger SLC9B2, also known as NHA2, correlates with the long-sought-after Na<jats:sup>+</jats:sup>/Li<jats:sup>+</jats:sup> 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<jats:sup>+</jats:sup>/H<jats:sup>+</jats:sup> 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.</jats:p>

収録刊行物

参考文献 (87)*注記

もっと見る

関連プロジェクト

もっと見る

キーワード

詳細情報 詳細情報について

問題の指摘

ページトップへ