7P1I
Cryo EM structure of bison NHA2 in detergent and N-terminal extension helix
Summary for 7P1I
| Entry DOI | 10.2210/pdb7p1i/pdb |
| EMDB information | 13161 |
| Descriptor | mitochondrial sodium/hydrogen exchanger 9B2 (1 entity in total) |
| Functional Keywords | membrane protein sodium proton transporter, transport protein |
| Biological source | Bison bison (American bison) |
| Total number of polymer chains | 2 |
| Total formula weight | 114838.41 |
| Authors | Matsuoka, R.,Fudim, R.,Jung, S.,Drew, D. (deposition date: 2021-07-01, release date: 2022-01-26, Last modification date: 2024-07-17) |
| Primary citation | 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 Cited by 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: 35173351DOI: 10.1038/s41594-022-00738-2 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3.15 Å) |
Structure validation
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