Biology Reference
In-Depth Information
Figure 15.1 Domain structure of the Gelsolin/villin superfamily. (A colour reproduction
of this figure can be found in the colour plate section)
The solution structure of the amino-terminal domain of villin (14T, amino
acids 1-126) has been determined by heteronuclear resonance spectroscopy. A
central b-sheet with four antiparallel strands and a fifth parallel strand on one
edge forms the core structure which is surrounded by amphipathic helices, two
on one side and a two-stranded parallel b-sheet with another helix on the
other side. Mutational analyses of villin suggest that the actin-binding region
is localized near the parallel strand at the edge of the central b-sheet. Recently,
the NMR structure of the 35 C-terminal residues of chicken villin was
established (Simenel et al., 1995). This sequence forms an autonomously
folding subdomain which comprises three helices. The hydrophobic side
chains of
the three helices contribute to a compact hydrophobic core
structure.
Villin contains at least three actin-binding sites, two of which are Ca
2+
dependent and located on the core domain (Kd value: 7 mM). The third one,
Ca
2+
independent, is situated on the headpiece domain (Kd values: 0.3 mM).
Villin sequences involved in F-actin binding have been mapped using synthetic
peptides. A cluster of charged amino acids located at the interdomain region
of domains 1-2 (amino acids 133-147) is part of the F-actin binding site of the
core domain. Two rapidly exchanging Ca
2+
-binding sites have been
determined, one located in the core domain (Kd ΒΌ 3.510
6
M) and one in
