Sökning: WFRF:(Javaherian Anoosh D.)
> (2011) >
Metal-driven operat...
Metal-driven operation of the human large-conductance voltage- and Ca2+-dependent potassium channel (BK) gating ring apparatus
-
- Javaherian, Anoosh D. (författare)
- Division of Molecular Medicine, Department of Anesthesiolog, David Geffen School of Medicine, UCLA, Los Angeles, USA
-
- Yusifov, Taleh (författare)
- Division of Molecular Medicine, Department of Anesthesiolog, David Geffen School of Medicine, UCLA, Los Angeles, USA
-
- Pantazis, Antonios (författare)
- Division of Molecular Medicine, Department of Anesthesiolog, David Geffen School of Medicine, UCLA, Los Angeles, USA
-
visa fler...
-
- Franklin, Sarah (författare)
- Division of Molecular Medicine, Department of Anesthesiolog, David Geffen School of Medicine, UCLA, Los Angeles, USA
-
- Gandhi, Chris S. (författare)
- Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, California, USA
-
- Olcese, Riccardo (författare)
- ivision of Molecular Medicine, Department of Anesthesiology, Cardiovascular Research Laboratory, and Brain Research Institute, David Geffen School of Medicine, UCLA, Los Angeles, California, USA
-
visa färre...
-
(creator_code:org_t)
- American Society for Biochemistry and Molecular Biology, 2011
- 2011
- Engelska.
-
Ingår i: Journal of Biological Chemistry. - : American Society for Biochemistry and Molecular Biology. - 0021-9258 .- 1083-351X. ; 286:23, s. 20701-20709
- Relaterad länk:
-
https://urn.kb.se/re...
-
visa fler...
-
https://doi.org/10.1...
-
visa färre...
Abstract
Ämnesord
Stäng
- 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.
Ämnesord
- NATURVETENSKAP -- Biologi -- Strukturbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Structural Biology (hsv//eng)
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
Hitta via bibliotek
Till lärosätets databas