105 research outputs found
A Common Ca2+-Driven Interdomain Module Governs Eukaryotic NCX Regulation
Na+/Ca2+ exchanger (NCX) proteins mediate Ca2+-fluxes across the cell membrane to maintain Ca2+ homeostasis in many cell types. Eukaryotic NCX contains Ca2+-binding regulatory domains, CBD1 and CBD2. Ca2+ binding to a primary sensor (Ca3-Ca4 sites) on CBD1 activates mammalian NCXs, whereas CALX, a Drosophila NCX ortholog, displays an inhibitory response to regulatory Ca2+. To further elucidate the underlying regulatory mechanisms, we determined the 2.7 Å crystal structure of mammalian CBD12-E454K, a two-domain construct that retains wild-type properties. In conjunction with stopped-flow kinetics and SAXS (small-angle X-ray scattering) analyses of CBD12 mutants, we show that Ca2+ binding to Ca3-Ca4 sites tethers the domains via a network of interdomain salt-bridges. This Ca2+-driven interdomain switch controls slow dissociation of “occluded” Ca2+ from the primary sensor and thus dictates Ca2+ sensing dynamics. In the Ca2+-bound conformation, the interdomain angle of CBD12 is very similar in NCX and CALX, meaning that the interdomain distances cannot account for regulatory diversity in NCX and CALX. Since the two-domain interface is nearly identical among eukaryotic NCXs, including CALX, we suggest that the Ca2+-driven interdomain switch described here represents a general mechanism for initial conduction of regulatory signals in NCX variants
Chemistry and the Science of Transformation in Mary Shelley’s Frankenstein
This essay reads the novel in a new way, examining the way that Victor Frankenstein's chemical education (he does not train to be a doctor!) enables his creation of the monster. It reveals that chemists of the period had a different worldview to others where they saw the world in constant transformation and flux. I have written this essay co-written the introduction to the special issue, and co-edited the whole
The mechanism of sodium and substrate release from the binding pocket of vSGLT. Nature 468
Le livre de l'infirmière : adapté de l'anglais, d'après Miss Oxford (3e édition revue et augmentée) / L. Chaptal,... ; préface par le professeur M. Letulle
Appartient à l’ensemble documentaire : GCGen1Contient une table des matièresAvec mode text
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