Biology Reference
In-Depth Information
Figure 3.4 The MyoK GPR loop contains multiple protein-protein interaction motifs.
(A) The 148 residues domain is extremely rich in Gly, Pro and Arg (64% total). (B) Profilin
has been shown to interact with poly-Pro stretches and ZPPF motifs (Witke et al., 2001)
and SH3 domain containing proteins are known to interact with motifs of either RxxPxxP
(class I) or PxxPxR (class II) motifs. These motifs are boxed in (A). Note the overlapping
distribution of some motifs in the middle of the GPR domain, that could potentially lead to
competition for and/or hierarchy of binding (C)
(Figure 3.4A) that have been shown to work as profilin-binding sites (for
example ZPPF, Figure 3.4B (Witke et al., 2001)). Finally, it contains a
canonical class I SH3 binding motif (RxxPxxP). The GPR-loop might therefore
serve as a multifunctional protein-protein interaction domain (Figure 3.4C)
and it is not known yet whether the different, sometimes overlapping, binding
sites lead to competition and/or hierarchy of binding events. First biochemical
analysis indicated that MyoK has two independent actin-binding sites (one
ATP-dependent and one salt-sensitive), suggesting that it may act as a novel
Figure 3.3 (opposite) Structure of class I myosins in D. discoideum. (A) The ameboid
myosins are either long-tailed (like MyoB) or short-tailed (like MyoA), but MyoK has a
more exotic architecture. It has a very short neck/tail domain, its C-terminus is
carboxymethyl-farnesylated, and it bears a 150-residue insertion in a surface loop of the
motor domain otherwise well conserved in length. This extended loop 1 is extremely rich in
Gly, Pro organized in pseudo repeats punctuated by the positive charges of Arg, and is thus
called GPR loop. This composition is very similar to the TH2 domains of other class I
myosins (B), even though the relative densities of Gly and Pro change, and Arg is
sometimes replaced by double Lys (as in MyoC). In addition, the GPR loop of MyoK
bears high sequence similarity with the Pro-rich domains (PRD) of WASp family members,
for example, it has about 40% identity and over 60% homology with the PRD of mouse
WASp (C)
