Model for the interaction of amphiphilic helices with troponin C and calmodulin.
Crystals of troponin C are stabilized by an intermolecular interaction that involves the packing of helix A from the N-terminal domain of one molecule onto the exposed hydrophobic cleft of the C-terminal domain of a symmetry related molecule. Analysis of this molecular recognition interaction in troponin C suggests a possible mode for the binding of amphiphilic helical molecules to troponin C and to calmodulin. From the template provided by this troponin C packing, it has been possible to build a model of the contact region of mastoporan as it might be bound to the two Ca2+ binding proteins. A possible binding mode of melittin to calmodulin is also proposed. Although some of the characteristics of binding are similar for the two amphiphilic peptides, the increased length of melittin requires a significant bend in the calmodulin central helix similar to that suggested recently for the myosin light chain kinase calmodulin binding peptide (Persechini and Kretsinger: Journal of Cardiovascular Pharmacology 12:501-512, 1988). Not only are the hydrophobic interactions important in this model, but there are several favorable electrostatic interactions that are predicted as a result of the molecular modeling. The regions of troponin-C and calmodulin to which amphiphilic helices bind are similar to the regions to which the neuroleptic drugs such as trifluoperazine have been predicted to bind (Strynadka and James: Proteins 3:1-17, 1988).
Strynadka
N C
NC
Department of Biochemistry, University of Alberta, Edmonton, Canada.
James
M N
MN
D000595:Amino Acid Sequence; D000818:Animals; D002147:Calmodulin; D003198:Computer Simulation; D036341:Intercellular Signaling Peptides and Proteins; D008555:Melitten; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010455:Peptides; D011487:Protein Conformation; D014336:Troponin; D019209:Troponin C; D014422:Turkeys; D014862:Wasp Venoms; D014867:Water; D014961:X-Ray Diffraction
D002147:Calmodulin; D036341:Intercellular Signaling Peptides and Proteins; D010455:Peptides; D014336:Troponin; D019209:Troponin C; D014862:Wasp Venoms; D014867:Water; D008555:Melitten; C037500:mastoparan