Melittin is the principal protein component of the venom of the honeybee, Apis mellifera. It inhibits protein kinase C, Ca2+/calmodulin-dependent protein kinase II, myosin light chain kinase and Na+/K+-ATPase (synaptosomal membrane) and is a cell membrane lytic factor. Melittin is a small peptide with no disulphide bridge; the N-terminal part of the molecule is predominantly hydrophobic and the C-terminal part is hydrophilic and strongly basic. The molecular mechanisms underlying the various effects of melittin on membranes have not been completely defined and much of the evidence indicates that different molecular mechanisms may underlie different actions of the peptide [PMID: 2187536]. Extensive work with melittin has shown that the venom has multiple effects, probably, as a result of its interaction with negatively changed phospholipids. It inhibits well known transport pumps such as the Na+-K+-ATPase and the H+-K+-ATPase. Melittin increases the permeability of cell membranes to ions, particularly Na+ and indirectly Ca2+, because of the Na+-Ca2+-exchange. This effect results in marked morphological and functional changes, particularly in excitable tissues such as cardiac myocytes. In some other tissues, e.g., cornea, not only Na+ but Cl- permeability is also increased by melittin. [PMID: 10072885]. The study of melittin in model membranes has been useful for the development of methodology for determination of membrane protein structures. A molecular dynamics simulation of melittin in a hydrated dipalmitoylphosphatidylcholine (DPPC) bilayer was carried out. The effect of melittin on the surrounding membrane was localised to its immediate vicinity, and its asymmetry with respect to the two layers may be a result of the fact that it is not fully transmembranal. Melittin's hydrophilic C terminus anchors it at the extracellular interface, leaving the N terminus "loose" in the lower layer of the membrane [PMID: 10692322].