Linked Life Data

9609707

Source:http://linkedlifedata.com/resource/pubmed/id/9609707

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
22
pubmed:dateCreated
1998-6-22
pubmed:databankReference
pubmed:abstractText
IsK (minK) protein, in concert with another channel protein KVLQT1, mediates a distinct, slowly activating, voltage-gated potassium current across certain mammalian cell membranes. Site-directed mutational studies have led to the proposal that the single transmembrane segment of IsK participates in the pore of the potassium channel [Takumi, T. (1993) News Physiol. Sci. 8, 175-178]. We present functional and structural studies of a short peptide (K27) with primary structure NH2-1KLEALYILMVLGFFGFFTLGIMLSYI27R-COOH, corresponding to the transmembrane segment of IsK (residues 42-68). When K27 was incorporated, at low concentrations, into phosphatidylethanolamine, black-lipid membranes, single-channel activity was observed, with no strong ion selectivity. IR measurements reveal the peptide has a predominantly helical conformation in the membrane. The atomic resolution structure of the helix has been established by high-resolution 1H NMR spectroscopy studies. These studies were carried out in a solvent comprising 86% v/v 1,1,1,3,3,3-hexafluoro-isopropanol-14% v/v water, in which the IR spectrum of the peptide was found to be very similar to that observed in the bilayer. The NMR studies have established that residues 1-3 are disordered, while residues 4-27 have an alpha-helical conformation, the helix being looser near the termini and more stable in the central region of the molecule. The length (2. 6 nm) of the hydrophobic segment of the helix, residues 7-23, matches the span of the hydrocarbon chains (2.3 +/- 0.25 nm) of fully hydrated bilayers of phosphatidylcholine lipid mixture from egg yolk. The side chains on the helix surface are predominantly hydrophobic, consistent with a transmembrane location of the helix. The ion-channeling activity is believed to stem from long-lived aggregates of these helices. The aggregation is mediated by the pi-pi stacking of phenylalanine aromatic rings of adjacent helices and favorable interactions of the opposing aliphatic-like side chains, such as leucine and methionine, with the lipid chains of the bilayer. This mechanism is in keeping with site-directed mutational studies which suggest that the transmembrane segment of IsK is an integral part of the pore of the potassium channel and has a similar disposition to that in the peptide model system.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0006-2960
pubmed:author
pubmed:issnType
Print
pubmed:day
2
pubmed:volume
37
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
8121-31
pubmed:dateRevised
2009-9-29
pubmed:meshHeading
pubmed-meshheading:9609707-Amino Acid Sequence, pubmed-meshheading:9609707-Circular Dichroism, pubmed-meshheading:9609707-Egg Yolk, pubmed-meshheading:9609707-Electric Conductivity, pubmed-meshheading:9609707-Lipid Bilayers, pubmed-meshheading:9609707-Magnetic Resonance Spectroscopy, pubmed-meshheading:9609707-Membrane Proteins, pubmed-meshheading:9609707-Models, Molecular, pubmed-meshheading:9609707-Molecular Sequence Data, pubmed-meshheading:9609707-Peptide Fragments, pubmed-meshheading:9609707-Peptides, pubmed-meshheading:9609707-Phosphatidylcholines, pubmed-meshheading:9609707-Potassium Channels, pubmed-meshheading:9609707-Potassium Channels, Voltage-Gated, pubmed-meshheading:9609707-Protein Conformation, pubmed-meshheading:9609707-Solvents, pubmed-meshheading:9609707-Spectroscopy, Fourier Transform Infrared
pubmed:year
1998
pubmed:articleTitle
Conformation and ion-channeling activity of a 27-residue peptide modeled on the single-transmembrane segment of the IsK (minK) protein.
pubmed:affiliation
Centre for Self-Organising Molecular Systems, University of Leeds, U.K.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't