TY - JOUR
T1 - Structure, location, and lipid perturbations of melittin at the membrane interface
AU - Hristova, Kalina
AU - Dempsey, Christopher E.
AU - White, Stephen H.
N1 - Funding Information:
This research was supported in part by a grant from the National Institutes of Health (GM-46823). We thank Drs. William Wimley and Alexey Ladokhin for many helpful conversations.
PY - 2001
Y1 - 2001
N2 - Melittin is arguably the most widely studied amphipathic, membrane-lytic α-helical peptide. Although several lines of evidence suggest an interfacial membrane location at low concentrations, melittin's exact position and depth of penetration into the hydrocarbon core are unknown. Furthermore, the structural basis for its lytic action remains largely a matter of conjecture. Using a novel x-ray absolute-scale refinement method, we have now determined the location, orientation, and likely conformation of monomeric melittin in oriented phosphocholine lipid multilayers. Its helical axis is aligned parallel to the bilayer plane at the depth of the glycerol groups, but its average conformation differs from the crystallographic structure. As observed earlier for another amphipathic α-helical peptide, the lipid perturbations induced by melittin are remarkably modest. Small bilayer perturbations thus appear to be a general feature of amphipathic helices at low concentrations. In contrast, a dimeric form of melittin causes larger structural perturbations under otherwise identical conditions. These results provide direct structural evidence that self-association of amphipathic helices may be the crucial initial step toward membrane lysis.
AB - Melittin is arguably the most widely studied amphipathic, membrane-lytic α-helical peptide. Although several lines of evidence suggest an interfacial membrane location at low concentrations, melittin's exact position and depth of penetration into the hydrocarbon core are unknown. Furthermore, the structural basis for its lytic action remains largely a matter of conjecture. Using a novel x-ray absolute-scale refinement method, we have now determined the location, orientation, and likely conformation of monomeric melittin in oriented phosphocholine lipid multilayers. Its helical axis is aligned parallel to the bilayer plane at the depth of the glycerol groups, but its average conformation differs from the crystallographic structure. As observed earlier for another amphipathic α-helical peptide, the lipid perturbations induced by melittin are remarkably modest. Small bilayer perturbations thus appear to be a general feature of amphipathic helices at low concentrations. In contrast, a dimeric form of melittin causes larger structural perturbations under otherwise identical conditions. These results provide direct structural evidence that self-association of amphipathic helices may be the crucial initial step toward membrane lysis.
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U2 - 10.1016/S0006-3495(01)76059-6
DO - 10.1016/S0006-3495(01)76059-6
M3 - Article
C2 - 11159447
AN - SCOPUS:0035144532
SN - 0006-3495
VL - 80
SP - 801
EP - 811
JO - Biophysical journal
JF - Biophysical journal
IS - 2
ER -