1b4i: Difference between revisions

Revision as of 12:51, 21 February 2008

CONTROL OF K+ CHANNEL GATING BY PROTEIN PHOSPHORYLATION: STRUCTURAL SWITCHES OF THE INACTIVATION GATE, NMR, 22 STRUCTURES

OverviewOverview

Fast N-type inactivation of voltage-dependent potassium (Kv) channels controls membrane excitability and signal propagation in central neurons and occurs by a 'ball-and-chain'-type mechanism. In this mechanism an N-terminal protein domain (inactivation gate) occludes the pore from the cytoplasmic side. In Kv3.4 channels, inactivation is not fixed but is dynamically regulated by protein phosphorylation. Phosphorylation of several identified serine residues on the inactivation gate leads to reduction or removal of fast inactivation. Here, we investigate the structure-function basis of this phospho-regulation with nuclear magnetic resonance (NMR) spectroscopy and patch-clamp recordings using synthetic inactivation domains (ID). The dephosphorylated ID exhibited compact structure and displayed high-affinity binding to its receptor. Phosphorylation of serine residues in the N- or C-terminal half of the ID resulted in a loss of overall structural stability. However, depending on the residue(s) phosphorylated, distinct structural elements remained stable. These structural changes correlate with the distinct changes in binding and unbinding kinetics underlying the reduced inactivation potency of phosphorylated IDs.

About this StructureAbout this Structure

1B4I is a Single protein structure of sequence from Escherichia coli. Full crystallographic information is available from OCA.

ReferenceReference

Control of K+ channel gating by protein phosphorylation: structural switches of the inactivation gate., Antz C, Bauer T, Kalbacher H, Frank R, Covarrubias M, Kalbitzer HR, Ruppersberg JP, Baukrowitz T, Fakler B, Nat Struct Biol. 1999 Feb;6(2):146-50. PMID:10048926

Page seeded by OCA on Thu Feb 21 11:51:24 2008

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA

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-[[Image:1b4i.gif|left|200px]]<br />
+[[Image:1b4i.gif|left|200px]]<br /><applet load="1b4i" size="350" color="white" frame="true" align="right" spinBox="true"
-<applet load="1b4i" size="450" color="white" frame="true" align="right" spinBox="true"
 caption="1b4i" />
 '''CONTROL OF K+ CHANNEL GATING BY PROTEIN PHOSPHORYLATION: STRUCTURAL SWITCHES OF THE INACTIVATION GATE, NMR, 22 STRUCTURES'''<br />
 ==Overview==
-Fast N-type inactivation of voltage-dependent potassium (Kv) channels, controls membrane excitability and signal propagation in central neurons, and occurs by a 'ball-and-chain'-type mechanism. In this mechanism an, N-terminal protein domain (inactivation gate) occludes the pore from the, cytoplasmic side. In Kv3.4 channels, inactivation is not fixed but is, dynamically regulated by protein phosphorylation. Phosphorylation of, several identified serine residues on the inactivation gate leads to, reduction or removal of fast inactivation. Here, we investigate the, structure-function basis of this phospho-regulation with nuclear magnetic, resonance (NMR) spectroscopy and patch-clamp recordings using synthetic, inactivation domains (ID). The dephosphorylated ID exhibited compact, structure and displayed high-affinity binding to its receptor., Phosphorylation of serine residues in the N- or C-terminal half of the ID, resulted in a loss of overall structural stability. However, depending on, the residue(s) phosphorylated, distinct structural elements remained, stable. These structural changes correlate with the distinct changes in, binding and unbinding kinetics underlying the reduced inactivation potency, of phosphorylated IDs.
+Fast N-type inactivation of voltage-dependent potassium (Kv) channels controls membrane excitability and signal propagation in central neurons and occurs by a 'ball-and-chain'-type mechanism. In this mechanism an N-terminal protein domain (inactivation gate) occludes the pore from the cytoplasmic side. In Kv3.4 channels, inactivation is not fixed but is dynamically regulated by protein phosphorylation. Phosphorylation of several identified serine residues on the inactivation gate leads to reduction or removal of fast inactivation. Here, we investigate the structure-function basis of this phospho-regulation with nuclear magnetic resonance (NMR) spectroscopy and patch-clamp recordings using synthetic inactivation domains (ID). The dephosphorylated ID exhibited compact structure and displayed high-affinity binding to its receptor. Phosphorylation of serine residues in the N- or C-terminal half of the ID resulted in a loss of overall structural stability. However, depending on the residue(s) phosphorylated, distinct structural elements remained stable. These structural changes correlate with the distinct changes in binding and unbinding kinetics underlying the reduced inactivation potency of phosphorylated IDs.
 ==About this Structure==
-B4I is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1B4I OCA].
+B4I is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1B4I OCA].
 ==Reference==
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 [[Category: Frank, R.]]
 [[Category: Kalbacher, H.]]
-[[Category: Kalbitzer, H.R.]]
+[[Category: Kalbitzer, H R.]]
-[[Category: Ruppersberg, J.P.]]
+[[Category: Ruppersberg, J P.]]
 [[Category: inactivation gate]]
 [[Category: phosphorylation]]
 [[Category: potassium channel]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 16:05:41 2007''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 11:51:24 2008''