Zn2+ ions selectively induce antimicrobial salivary peptide histatin-5 to fuse negatively charged vesicles. Identification and characterization of a zinc-binding motif present in the functional domain
S. Melino et al., Zn2+ ions selectively induce antimicrobial salivary peptide histatin-5 to fuse negatively charged vesicles. Identification and characterization of a zinc-binding motif present in the functional domain, BIOCHEM, 38(30), 1999, pp. 9626-9633
The salivary antimicrobial peptide histatin-5 is able to aggregate and fuse
negatively charged small unilamellar vesicles, and this fusogenic activity
is selectively induced by the presence of zinc ions. Circular dichroism sp
ectroscopy shows that histatin-5, in the presence of negatively charged ves
icles and zinc ions, undergoes a conformational change leading to the stabi
lization of an ct-helical secondary structure. We attribute the specific ac
tion of the zinc ions to the presence of a consensus sequence, HEXXH, locat
ed in the C-terminal functional domain of histatin-5, a recognized zinc-bin
ding motif in many proteins. Two-dimensional proton NMR spectroscopy of his
tatin-5 in a trifluoroethanol/water mixture (a membrane mimetic environment
) has been performed and the results analyzed by means of distance geometry
and restrained molecular dynamics simulations. Our results reveal that the
peptide chain, including the Zn-binding consensus sequence corresponding t
o residues 15-19, is in a helicoidal conformation. Comparison of the chemic
al shifts of the individual amino acids in histatin-5 with those recently r
eported in other solvents indicates that trifluoroethanol/water has a struc
turing capability somewhere between water and dimethyl sulfoxide. The mecha
nism of action of this antimicrobial peptide is discussed on the basis of i
ts structural characteristics with particular attention to the Zn-binding m
otif.