9Z4I
Cryo-EM structure of the mitochondrial NCLX in its monomeric state
Summary for 9Z4I
| Entry DOI | 10.2210/pdb9z4i/pdb |
| EMDB information | 73804 |
| Descriptor | Mitochondrial sodium/calcium exchanger protein, SODIUM ION (2 entities in total) |
| Functional Keywords | nclx, exchanger, membrane protein |
| Biological source | Rattus norvegicus (Norway rat) |
| Total number of polymer chains | 1 |
| Total formula weight | 67405.22 |
| Authors | |
| Primary citation | Zhang, L.,Han, Y.,Zeng, W.,Xue, J.,Wang, Y.,Jiang, Y. Molecular mechanisms of mitochondrial Ca 2+ exchanger NCLX. Nat Commun, 17:-, 2026 Cited by PubMed Abstract: Mitochondrial Ca²⁺ homeostasis is maintained through coordinated influx and efflux processes, with NCLX long recognized as the primary Ca²⁺ extruder operating via Na⁺/Ca²⁺ exchange. Here, we report cryo-EM structures of rat NCLX in cytosolic-facing occluded and open states. The central transmembrane (TM) domain of NCLX comprises ten helices arranged in two inverted, structurally similar halves, with two α-repeats forming a central ion-binding pocket. Peripheral TMs 1 and 6 are loosely associated with the core and likely mediate alternative access to this site. These structural features closely resemble those of NCXs, indicating a conserved ion exchange mechanism. While NCLX retains the canonical Ca²⁺-binding site, it lacks several key Na⁺-binding residues found in NCXs, suggesting broader ion selectivity. Consistently, cell-based Ca²⁺ uptake assays show that NCLX mediates Ca²⁺ exchange using Na⁺, K⁺, Li⁺, and potentially protons as counterions. Based on the structural symmetry of NCLX and its bidirectional exchange capability, we propose a matrix-facing model and an alternating-access mechanism in which TMs 1 and 6 undergo sliding motions to enable ion exchange between cytosolic and matrix sides, analogous to NCX. These findings provide a structural and mechanistic framework for understanding NCLX-mediated Ca²⁺ transport in mitochondria. PubMed: 42431881DOI: 10.1038/s41467-026-75483-x PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3.62 Å) |
Structure validation
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