title: Quantitative interactions between cryptdin-4 amino terminal variants and membranes.
abstract: Paneth cells secrete alpha-defensins into the lumen from the base of small intestinal crypts, and cryptdin-4 (Crp4) is the most potent mouse alpha-defensin in vitro. Purified recombinant Crp4 and Crp4 variants with (des-Gly)-, (Gly1Val)-, (Gly1Asp)-, and (Gly1Arg)-substitutions were all bactericidal with Crp4 and (Gly1Arg)-Crp4 being slightly more active than other variants. Bactericidal activities correlated directly with permeabilization of live Escherichia coli, with equilibrium binding to E. coli membrane phospholipid bilayers and vesicles, and with induced graded fluorophore leakage from phospholipid vesicles. The Crp4 peptide N-terminus affects bactericidal activity modestly, apparently by influencing peptide binding to phospholipid bilayers and subsequent permeabilization of target cell membranes.
authors.affiliation: Department of Pathology, College of Medicine, University of California, Irvine, CA 92697-4800, USA.
authors.forename: Donald P
authors.initials: DP
authors.lastname: Satchell
authors.forename: Tanya
authors.initials: T
authors.lastname: Sheynis
authors.forename: Sofiya
authors.initials: S
authors.lastname: Kolusheva
authors.forename: Jason
authors.initials: J
authors.lastname: Cummings
authors.forename: T Kyle
authors.initials: TK
authors.lastname: Vanderlick
authors.forename: Raz
authors.initials: R
authors.lastname: Jelinek
authors.forename: Michael E
authors.initials: ME
authors.lastname: Selsted
authors.forename: Andre J
authors.initials: AJ
authors.lastname: Ouellette
mesh_terms: D000114:Acetylene / Q000031:analogs & derivatives* / Q000378:metabolism; D019943:Amino Acid Substitution / Q000235:genetics; D000818:Animals; D002462:Cell Membrane / Q000378:metabolism*; D002463:Cell Membrane Permeability / Q000187:drug effects; D005658:Fungi / Q000187:drug effects; D006090:Gram-Negative Bacteria / Q000187:drug effects; D006094:Gram-Positive Bacteria / Q000187:drug effects; D008081:Liposomes / Q000737:chemistry / Q000378:metabolism; D051379:Mice; D010743:Phospholipids / Q000378:metabolism; D000078789:Polyacetylene Polymer; D011108:Polymers / Q000378:metabolism; D053279:Polyynes; D011994:Recombinant Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism / Q000494:pharmacology; D023084:alpha-Defensins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D008081:Liposomes; D010743:Phospholipids; D000078789:Polyacetylene Polymer; D011108:Polymers; D011994:Recombinant Proteins; D023084:alpha-Defensins; C401847:cryptdin 4, mouse; D053279:Polyynes; C082361:polydiacetylene; D000114:Acetylene