title: Interaction of cardiotoxins with membranes: a molecular modeling study.
abstract: Incorporation of beta-sheet proteins into membrane is studied theoretically for the first time, and the results are validated by the direct experimental data. Using Monte Carlo simulations with implicit membrane, we explore spatial structure, energetics, polarity, and mode of insertion of two cardiotoxins with different membrane-destabilizing activity. Both proteins, classified as P- and S-type cardiotoxins, are found to retain the overall "three-finger" fold interacting with membrane core and lipid/water interface by the tips of the "fingers" (loops). The insertion critically depends upon the structure, hydrophobicity, and electrostatics of certain regions. The simulations reveal apparently distinct binding modes for S- and P-type cardiotoxins via the first loop or through all three loops, respectively. This rationalizes an earlier empirical classification of cardiotoxins into S- and P-type, and provides a basis for the analysis of experimental data on their membrane affinities. Accomplished with our previous simulations of membrane alpha-helices, the computational method may be used to study partitioning of proteins with diverse folds into lipid bilayers.
authors.affiliation: M. M. Shemyakin & Yu. A. Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow V-437, 117997 GSP, Russia. efremov@nmr.ru
authors.forename: Roman G
authors.initials: RG
authors.lastname: Efremov
authors.forename: Pavel E
authors.initials: PE
authors.lastname: Volynsky
authors.forename: Dmitry E
authors.initials: DE
authors.lastname: Nolde
authors.forename: Peter V
authors.initials: PV
authors.lastname: Dubovskii
authors.forename: Alexander S
authors.initials: AS
authors.lastname: Arseniev
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001703:Biophysics / Q000379:methods; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism*; D004179:Cobra Cardiotoxin Proteins / Q000737:chemistry*; D017815:Elapidae; D008051:Lipid Bilayers; D008823:Micelles; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009010:Monte Carlo Method; D011485:Protein Binding; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D017386:Sequence Homology, Amino Acid; D012984:Software
chemical_list: D004179:Cobra Cardiotoxin Proteins; D008051:Lipid Bilayers; D008823:Micelles