8sgt

Cryo-EM structure of human NCX1 in Ca2+ bound, activated state (group II in the presence of 0.5 mM Ca2+)

spinqualitylabelsall models 8sgt, resolution 3.60Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8sgt is a 3 chain structure with sequence from Homo sapiens and Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 3.6Å Ligands: CA Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed Na(+)/Ca(2+) exchangers (NCX) transport Ca(2+) in or out of cells in exchange for Na(+). They are ubiquitously expressed and play an essential role in maintaining cytosolic Ca(2+) homeostasis. Although extensively studied, little is known about the global structural arrangement of eukaryotic NCXs and the structural mechanisms underlying their regulation by various cellular cues including cytosolic Na(+) and Ca(2+). Here we present the cryo-EM structures of human cardiac NCX1 in both inactivated and activated states, elucidating key structural elements important for NCX ion exchange function and its modulation by cytosolic Ca(2+) and Na(+). We demonstrate that the interactions between the ion-transporting transmembrane (TM) domain and the cytosolic regulatory domain define the activity of NCX. In the inward-facing state with low cytosolic [Ca(2+)], a TM-associated four-stranded beta-hub mediates a tight packing between the TM and cytosolic domains, resulting in the formation of a stable inactivation assembly that blocks the TM movement required for ion exchange function. Ca(2+) binding to the cytosolic second Ca(2+)-binding domain (CBD2) disrupts this inactivation assembly which releases its constraint on the TM domain, yielding an active exchanger. Thus, the current NCX1 structures provide an essential framework for the mechanistic understanding of the ion transport and cellular regulation of NCX family proteins. Structural mechanisms of the human cardiac sodium-calcium exchanger NCX1.,Xue J, Zeng W, Han Y, John S, Ottolia M, Jiang Y Nat Commun. 2023 Oct 4;14(1):6181. doi: 10.1038/s41467-023-41885-4. PMID:37794011 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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