Premium
Defensins promote fusion and lysis of negatively charged membranes
Author(s) -
Fujii Gary,
Eisenberg David,
Selsted Michael E.
Publication year - 1993
Publication title -
protein science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.353
H-Index - 175
eISSN - 1469-896X
pISSN - 0961-8368
DOI - 10.1002/pro.5560020813
Subject(s) - membrane , circular dichroism , liposome , biophysics , lysis , chemistry , amphiphile , lipid bilayer fusion , fusion , hydrophobic effect , biochemistry , biology , organic chemistry , polymer , linguistics , philosophy , copolymer
Defensins, a family of cationic peptides isolated from mammalian granulocytes and believed to permeabilize membranes, were tested for their ability to cause fusion and lysis of liposomes. Unlike α‐helical peptides whose lytic effects have been extensively studied, the defensins consist primarily of β‐sheet. Defensins fuse and lyse negatively charged liposomes but display reduced activity with neutral liposomes. These and other experiments suggest that fusion and lysis is mediated primarily by electrostatic forces and to a lesser extent, by hydrophobic interactions. Circular dichroism and fluorescence spectroscopy of native defensins indicate that the amphiphilic β‐sheet structure is maintained throughout the fusion process. Taken together, these results support the idea that protein‐mediated membrane fusion depends not only on hydrophobic and electrostatic forces but also on the spatial arrangement of the amino acid residues to form a three‐dimensional amphiphilic structure, which promotes the efficient mixing of the lipids between membranes. A molecular model for membrane fusion by defensins is presented, which takes into account the contributions of electrostatic forces, hydrophobic interactions, and structural amphiphilicity.