Structural and biophysical properties of a synthetic channel-forming peptide: designing a clinically relevant anion selective pore

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dc.contributor.author Bukovnik, U.
dc.contributor.author Gao, J.
dc.contributor.author Cook, G. A.
dc.contributor.author Shank, L. P.
dc.contributor.author Seabra, M. B.
dc.contributor.author Schultz, Bruce D.
dc.contributor.author Iwamoto, T.
dc.contributor.author Chen, J.
dc.contributor.author Tomich, John M.
dc.date.accessioned 2012-06-22T13:56:26Z
dc.date.available 2012-06-22T13:56:26Z
dc.date.issued 2012-06-22
dc.identifier.uri http://hdl.handle.net/2097/13951
dc.description.abstract The design, synthesis, modeling and in vitro testing of channel-forming peptides derived from the cys-loop superfamily of ligand-gated ion channels are part of an ongoing research focus. Over 300 different sequences have been prepared based on the M2 transmembrane segment of the spinal cord glycine receptor α-subunit. A number of these sequences are water-soluble monomers that readily insert into biological membranes where they undergo supramolecular assembly, yielding channels with a range of selectivities and conductances. Selection of a sequence for further modifications to yield an optimal lead compound came down to a few key biophysical properties: low solution concentrations that yield channel activity, greater ensemble conductance, and enhanced ion selectivity. The sequence NK[subscript]4-M2GlyR T19R, S22W (KKKKPARVGLGITTVLTMRTQW) addressed these criteria. The structure of this peptide has been analyzed by solution NMR as a monomer in detergent micelles, simulated as five-helix bundles in a membrane environment, modified by cysteine-scanning and studied for insertion efficiency in liposomes of selected lipid compositions. Taken together, these results define the structural and key biophysical properties of this sequence in a membrane. This model provides an initial scaffold from which rational substitutions can be proposed and tested to modulate anion selectivity. This article is part of a Special Issue entitled: Protein Folding in Membranes. en_US
dc.relation.uri http://www.sciencedirect.com/science/article/pii/S0005273611002422 en_US
dc.subject Channel-forming peptide en_US
dc.subject Self-assembly en_US
dc.subject Glycine receptor en_US
dc.subject Pore structure en_US
dc.title Structural and biophysical properties of a synthetic channel-forming peptide: designing a clinically relevant anion selective pore en_US
dc.type Article (author version) en_US
dc.date.published 2012 en_US
dc.citation.doi doi:10.1016/j.bbamem.2011.07.037 en_US
dc.citation.epage 1048 en_US
dc.citation.issue 4 en_US
dc.citation.jtitle Biochimica et Biophysica Acta – Biomembranes en_US
dc.citation.spage 1039 en_US
dc.citation.volume 1818 en_US
dc.contributor.authoreid ubkov en_US
dc.contributor.authoreid jcgao en_US
dc.contributor.authoreid bschultz en_US
dc.contributor.authoreid iwamoto en_US
dc.contributor.authoreid jtomich en_US

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