title: Conolysin-Mt: a conus peptide that disrupts cellular membranes.
abstract: Conus venoms are estimated to comprise over 100,000 distinct pharmacologically active peptides, the majority probably targeting ion channels. Through the characterization of a cytolytic peptide from the venom of Conus mustelinus, conolysin-Mt, we expand the known conopeptide mechanisms to include association with and destruction of cellular membranes. A new 23AA conopeptide, conolysin-Mt has potent hemolytic activity when tested on human erythrocytes. At a concentration of 0.25 microM, the peptide permeabilized both negatively charged prokaryotic (PE:PG) and zwitterionic eukaryotic (PC:cholesterol) model membranes. The affinity constants (KA) of conolysin-Mt for PE:PG and PC:cholesterol model membranes were 0.9 +/- 0.3 x 10(7) and 3 +/- 1 x 10(7) M-1, respectively. In contrast, conolysin-Mt exhibited low antimicrobial activity (MIC > 50 microM) against two Escherichia coli strains, with an MIC for the Gram-positive S. aureus of 25-50 microM. The specificity of conolysin-Mt for native eukaryotic membranes is a novel feature of the peptide compared to other well-characterized cytolytic peptides such as melittin.
authors.affiliation: Department of Biology, University of Utah, Salt Lake City, Utah 84108, USA.
authors.forename: Jason S
authors.initials: JS
authors.lastname: Biggs
authors.forename: Yosef
authors.initials: Y
authors.lastname: Rosenfeld
authors.forename: Yechiel
authors.initials: Y
authors.lastname: Shai
authors.forename: B M
authors.initials: BM
authors.lastname: Olivera
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002462:Cell Membrane / Q000737:chemistry* / Q000187:drug effects*; D020916:Conotoxins / Q000737:chemistry / Q000494:pharmacology*; D052078:Conus Snail; D003603:Cytotoxins / Q000494:pharmacology; D004341:Drug Evaluation; D005057:Eukaryotic Cells / Q000737:chemistry / Q000187:drug effects / Q000648:ultrastructure; D006801:Humans; D008555:Melitten / Q000737:chemistry; D051379:Mice; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology; D011387:Prokaryotic Cells / Q000737:chemistry / Q000187:drug effects / Q000648:ultrastructure; D017386:Sequence Homology, Amino Acid
chemical_list: D020916:Conotoxins; D003603:Cytotoxins; D010455:Peptides; C525557:conolysin-Mt, Conus mustelinus; D008555:Melitten