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Metal-driven operat...
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Javaherian, Anoosh D.Division of Molecular Medicine, Department of Anesthesiolog, David Geffen School of Medicine, UCLA, Los Angeles, USA
(författare)
Metal-driven operation of the human large-conductance voltage- and Ca2+-dependent potassium channel (BK) gating ring apparatus
- Artikel/kapitelEngelska2011
Förlag, utgivningsår, omfång ...
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American Society for Biochemistry and Molecular Biology,2011
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Nummerbeteckningar
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LIBRIS-ID:oai:DiVA.org:liu-162176
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https://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-162176URI
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https://doi.org/10.1074/jbc.M111.235234DOI
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Språk:engelska
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Sammanfattning på:engelska
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Ämneskategori:art swepub-publicationtype
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Large-conductance voltage- and Ca2+-dependent K+ (BK, also known as MaxiK) channels are homo-tetrameric proteins with a broad expression pattern that potently regulate cellular excitability and Ca2+ homeostasis. Their activation results from the complex synergy between the transmembrane voltage sensors and a large (>300 kDa) C-terminal, cytoplasmic complex (the “gating ring”), which confers sensitivity to intracellular Ca2+ and other ligands. However, the molecular and biophysical operation of the gating ring remains unclear. We have used spectroscopic and particle-scale optical approaches to probe the metal-sensing properties of the human BK gating ring under physiologically relevant conditions. This functional molecular sensor undergoes Ca2+- and Mg2+-dependent conformational changes at physiologically relevant concentrations, detected by time-resolved and steady-state fluorescence spectroscopy. The lack of detectable Ba2+-evoked structural changes defined the metal selectivity of the gating ring. Neutralization of a high-affinity Ca2+-binding site (the “calcium bowl”) reduced the Ca2+ and abolished the Mg2+ dependence of structural rearrangements. In congruence with electrophysiological investigations, these findings provide biochemical evidence that the gating ring possesses an additional high-affinity Ca2+-binding site and that Mg2+ can bind to the calcium bowl with less affinity than Ca2+. Dynamic light scattering analysis revealed a reversible Ca2+-dependent decrease of the hydrodynamic radius of the gating ring, consistent with a more compact overall shape. These structural changes, resolved under physiologically relevant conditions, likely represent the molecular transitions that initiate the ligand-induced activation of the human BK channel.
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Yusifov, TalehDivision of Molecular Medicine, Department of Anesthesiolog, David Geffen School of Medicine, UCLA, Los Angeles, USA
(författare)
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Pantazis, AntoniosDivision of Molecular Medicine, Department of Anesthesiolog, David Geffen School of Medicine, UCLA, Los Angeles, USA(Swepub:liu)antpa45
(författare)
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Franklin, SarahDivision of Molecular Medicine, Department of Anesthesiolog, David Geffen School of Medicine, UCLA, Los Angeles, USA
(författare)
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Gandhi, Chris S.Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, California, USA
(författare)
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Olcese, Riccardoivision of Molecular Medicine, Department of Anesthesiology, Cardiovascular Research Laboratory, and Brain Research Institute, David Geffen School of Medicine, UCLA, Los Angeles, California, USA
(författare)
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Division of Molecular Medicine, Department of Anesthesiolog, David Geffen School of Medicine, UCLA, Los Angeles, USADivision of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, California, USA
(creator_code:org_t)
Sammanhörande titlar
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Ingår i:Journal of Biological Chemistry: American Society for Biochemistry and Molecular Biology286:23, s. 20701-207090021-92581083-351X
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