3gin | pdb_00003gin

Crystal structure of E454K-CBD1

spinqualitylabelsall models 3gin, resolution 2.40Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3gin is a 2 chain structure with sequence from Canlf. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: CA Related: 2dpk, 2qvm Gene: SLC8A1 (CANLF) Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [NAC1_CANFA] Rapidly transports Ca(2+) during excitation-contraction coupling. Ca(2+) is extruded from the cell during relaxation so as to prevent overloading of intracellular stores. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed The mammalian Na(+)/Ca(2+) exchanger, NCX1.1, serves as the main mechanism for Ca(2+) efflux across the sarcolemma following cardiac contraction. In addition to transporting Ca(2+), NCX1.1 activity is also strongly regulated by Ca(2+) binding to two intracellular regulatory domains, CBD1 and CBD2. The structures of both of these domains have been solved by NMR spectroscopy and x-ray crystallography, greatly enhancing our understanding of Ca(2+) regulation. Nevertheless, the mechanisms by which Ca(2+) regulates the exchanger remain incompletely understood. The initial NMR study showed that the first regulatory domain, CBD1, unfolds in the absence of regulatory Ca(2+). It was further demonstrated that a mutation of an acidic residue involved in Ca(2+) binding, E454K, prevents this structural unfolding. A contradictory result was recently obtained in a second NMR study in which Ca(2+) removal merely triggered local rearrangements of CBD1. To address this issue, we solved the crystal structure of the E454K-CBD1 mutant and performed electrophysiological analyses of the full-length exchanger with mutations at position 454. We show that the lysine substitution replaces the Ca(2+) ion at position 1 of the CBD1 Ca(2+) binding site and participates in a charge compensation mechanism. Electrophysiological analyses show that mutations of residue Glu-454 have no impact on Ca(2+) regulation of NCX1.1. Together, structural and mutational analyses indicate that only two of the four Ca(2+) ions that bind to CBD1 are important for regulating exchanger activity. Structure and functional analysis of a Ca2+ sensor mutant of the Na+/Ca2+ exchanger.,Chaptal V, Ottolia M, Mercado-Besserer G, Nicoll DA, Philipson KD, Abramson J J Biol Chem. 2009 May 29;284(22):14688-92. Epub 2009 Mar 30. PMID:19332552 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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