Linked Life Data

12169104

Source:http://linkedlifedata.com/resource/pubmed/id/12169104

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2002-8-9
pubmed:abstractText
We have modelled the conformation of the III-IV loop of the Ca(v)2.1 subunit of P/Q calcium channels, a loop that is implicated in fast voltage-dependent inactivation. Change in channel inactivation requires its direct interaction with the I-II loop. This interaction occurs with an affinity in the order of 70 nm. Intracellular injection of a 40-mer III-IV loop-derived peptide produces an increase in the rate of fast inactivation. This alteration in channel kinetic is also accompanied by a hyperpolarizing shift in the steady-state voltage-dependence of inactivation. None of these effects are observed in the presence of a beta subunit, suggesting the existence of a competitive mechanism of action between the beta subunit and the III-IV loop. Amino acid sequence comparison using BLAST reveals that the III-IV loop shares 53% identity with the gamma subunit of G proteins. Because of the pivotal contribution of the III-IV loop to inactivation, an atomic model of the III-IV loop was generated by both homology modelling and molecular mechanics calculations. Using the X-ray structures of the betagamma dimer of the heterotrimeric G-proteins as templates, the III-IV loop is predicted to contain a well-structured alpha-helix at the amino-terminus with both the N- and C-termini having the same orientation in the plane of the inner lipid bilayer. We provide a hypothetical working model in which we propose that the III-IV loop interacts with the I-II loop via its Gbetagamma binding domain.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0953-816X
pubmed:author
pubmed:issnType
Print
pubmed:volume
16
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
219-28
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:12169104-Amino Acid Sequence, pubmed-meshheading:12169104-Animals, pubmed-meshheading:12169104-Binding Sites, pubmed-meshheading:12169104-Calcium Channels, N-Type, pubmed-meshheading:12169104-Calcium Signaling, pubmed-meshheading:12169104-Cell Membrane, pubmed-meshheading:12169104-Dose-Response Relationship, Drug, pubmed-meshheading:12169104-Female, pubmed-meshheading:12169104-Heterotrimeric GTP-Binding Proteins, pubmed-meshheading:12169104-Membrane Potentials, pubmed-meshheading:12169104-Models, Biological, pubmed-meshheading:12169104-Molecular Sequence Data, pubmed-meshheading:12169104-Neurons, pubmed-meshheading:12169104-Oocytes, pubmed-meshheading:12169104-Peptide Fragments, pubmed-meshheading:12169104-Protein Binding, pubmed-meshheading:12169104-Protein Structure, Tertiary, pubmed-meshheading:12169104-Recombinant Fusion Proteins, pubmed-meshheading:12169104-Synapses, pubmed-meshheading:12169104-Synaptic Transmission, pubmed-meshheading:12169104-Xenopus laevis
pubmed:year
2002
pubmed:articleTitle
Modelling of the III-IV loop, a domain involved in calcium channel Ca(v)2.1 inactivation, highlights a structural homology with the gamma subunit of G proteins.
pubmed:affiliation
Laboratoire de Biochimie, CNRS UMR 6560, Faculté de Médecine Nord, Boulevard Pierre Dramard, 13916 Marseille Cedex 20, France.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't