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-Structure paper
タイトル | Structure, mechanism and lipid-mediated remodeling of the mammalian Na/H exchanger NHA2. |
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ジャーナル・号・ページ | Nat Struct Mol Biol, Vol. 29, Issue 2, Page 108-120, Year 2022 |
掲載日 | 2022年2月16日 |
著者 | Rei Matsuoka / Roman Fudim / Sukkyeong Jung / Chenou Zhang / Andre Bazzone / Yurie Chatzikyriakidou / Carol V Robinson / Norimichi Nomura / So Iwata / Michael Landreh / Laura Orellana / Oliver Beckstein / David Drew / |
PubMed 要旨 | 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 ...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. |
リンク | Nat Struct Mol Biol / PubMed:35173351 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 3.04 - 3.64 Å |
構造データ | EMDB-13161, PDB-7p1i: EMDB-13162, PDB-7p1j: EMDB-13163, PDB-7p1k: EMDB-13597: |
化合物 | ChemComp-Y01: ChemComp-T7X: |
由来 |
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キーワード | TRANSPORT PROTEIN (運搬体タンパク質) / Membrane protein Sodium proton transporter (生体膜) |