Melittin
Melittin is the main component and the major pain-producing substance of honeybee venom. Melittin is a basic peptide consisting of 26 amino acids.
Function
The principal function of melittin as a component of bee venom is to cause pain and destruction of tissue of intruders that threaten a beehive. However, melittin is expressed, not only in the venom gland, but also in other tissues when the bee is infected with various pathogens. The over-expression of melittin in infected honey bees may indicate that it plays a role in the immune response of bees to infectious diseases.Structure
Melittin is a small peptide with no disulfide bridge; the N-terminal part of the molecule is predominantly hydrophobic and the C-terminal part is hydrophilic and strongly basic. In water, it forms a tetramer, but it also can spontaneously integrate itself into cell membranes.Mechanism of action
Injection of melittin into animals and humans causes pain sensations. It has strong surface effects on cell membranes, causing pore formation in epithelial cells and the destruction of red blood cells. Melittin also activates nociceptor cells through a variety of mechanisms.Melittin can open thermal nociceptor TRPV1 channels via cyclooxygenase metabolites, resulting in depolarization of nociceptor cells. The pore-forming effects in cells cause the release of pro-inflammatory cytokines. It also activates G-protein-coupled receptor-mediated opening of transient receptor potential channels. Finally, melittin up-regulates the expression of Nav1.8 and Nav1.9 sodium channels in nociceptor cell, causing long-term action-potential firing and pain sensation.
Melittin inhibits protein kinase C, Ca2+/calmodulin-dependent protein kinase II, myosin light chain kinase, and Na+/K+-ATPase. Melittin blocks transport pumps such as the Na+-K+-ATPase and the H+-K+-ATPase.