It is well known that the functions of
metalloproteins generally originate from their metal-binding motifs. However, the intrinsic nature of individual motifs remains unknown, particularly the details about metal-binding effects on the folding of motifs; the converse is also unknown, although there is no doubt that the motif is the core of the reactivity for each
metalloprotein. In this study, we focused our attention on the zinc-binding motif of the metzincin clan family, HEXXHXXGXXH; this family contains the general zinc-binding sequence His-Glu-Xaa-Xaa-His (HEXXH) and the extended GXXH region. We adopted the motif sequence of stromelysin-1 and investigated the folding properties of the Trp-labeled
peptides WAHEIAHSLGLFHA (STR-W1), AWHEIAHSLGLFHA (STR-W2), AHEIAHSLGWFHA (STR-W11), and AHEIAHSLGLFHWA (STR-W14) in the presence and absence of
zinc ions in hydrophobic micellar environments by
circular dichroism (CD) measurements. We accessed successful incorporation of these
zinc peptides into
micelles using
quenching of Trp
fluorescence. Results of CD studies indicated that two of the Trp-incorporated
peptides, STR-W1 and STR-W14, exhibited helical folding in the hydrophobic region of cetyltrimethylammonium
chloride micelle. The
NMR structural analysis of the apo STR-W14 revealed that the conformation in the
C-terminus GXXH region significantly differred between the apo state in the
micelle and the reported Zn-bound state of stromelysin-1 in
crystal structures. The structural analyses of the qualitative Zn-binding properties of this motif
peptide provide an interesting Zn-binding mechanism: the minimum consensus motif in the metzincin clan, a basic zinc-binding motif with an extended GXXH region, has the potential to serve as a preorganized Zn binding scaffold in a hydrophobic environment. Copyright (c) 2009 European
Peptide Society and John Wiley & Sons, Ltd.
