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9QUB

Cryo-EM structure of the human NHA2-Fab complex

Summary for 9QUB
Entry DOI10.2210/pdb9qub/pdb
EMDB information53377
DescriptorFab-light chain, Fab-heavy chain, Sodium/hydrogen exchanger 9B2, ... (4 entities in total)
Functional Keywordsna+/h+ exchanger, transport protein
Biological sourceHomo sapiens (Human)
More
Total number of polymer chains6
Total formula weight219466.40
Authors
Jung, S.,Drew, D. (deposition date: 2025-04-10, release date: 2025-05-14, Last modification date: 2025-05-28)
Primary citationJung, S.,Kokane, S.,Li, H.,Iwata, S.,Nomura, N.,Drew, D.
Structure and Inhibition of the Human Na + /H + Exchanger SLC9B2.
Int J Mol Sci, 26:-, 2025
Cited by
PubMed Abstract: The sodium/proton exchanger NHA2, also known as SLC9B2, is important for insulin secretion, renal blood pressure regulation, and electrolyte retention. Recent structures of bison NHA2 has revealed its unique 14-transmembrane helix architecture, which is different from SLC9A/NHE members made up from 13-TM helices. Sodium/proton exchangers are functional homodimers, and the additional N-terminal helix in NHA2 was found to alter homodimer assembly. Here, we present the cryo-electron microscopy structures of apo human NHA2 in complex with a Fab fragment and also with the inhibitor phloretin bound at 2.8 and 2.9 Å resolution, respectively. We show how phosphatidic acid (PA) lipids bind to the homodimer interface of NHA2 on the extracellular side, which we propose has a regulatory role linked to cell volume regulation. The ion binding site of human NHA2 has a salt bridge interaction between the ion binding aspartate D278 and R432, an interaction previously broken in the bison NHA2 structure, and these differences suggest a possible ion coupling mechanism. Lastly, the human NHA2 structure in complex with phloretin offers a template for structure-guided drug design, potentially leading to the development of more selective and potent NHA2 inhibitors.
PubMed: 40362458
DOI: 10.3390/ijms26094221
PDB entries with the same primary citation
Experimental method
ELECTRON MICROSCOPY (2.7 Å)
Structure validation

242842

数据于2025-10-08公开中

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