|
Figure 4.
Fig. 4. (a) Stereo view of the C-terminal region of C1
showing interactions of some of the key residues associated with
mutations, particularly Asp 228, Tyr237, Phe233 and Glu258. (c)
Alternative stereo view to (a) of the same region of C1 but
showing the surface locations of the Asp228 and Glu258 residues
where the mutations D228N and E258K occur, which radically alter
the surface charge. The overviews in (b) and (d) show the whole
C1 domain from the same viewing directions as (a) and (c),
respectively. (e and f) Schematic diagrams showing the possible
binding of (e) the myosin ELC extension and (f) the N-terminal
end of C0 and the Pro-Ala link (PA link) between domains C0 and
C1 in cMyBP-C to actin filaments through the actin-binding motif
(AB motif) whose sequence is given in Fig. 1e. In (e), coloured
in red are the myosin subfragment 2 (S2) and the neck and motor
of the myosin head. The myosin ELC and regulatory light chain
(RLC) are in orange and the Pro-Ala-rich extension on the ELC
(PA link) is in blue. A few actin monomers are shown in grey and
a tropomyosin strand (TM) in green. (f) This has the same myosin
and actin features as in (e), but here part of cMyBP-C is shown
with domains 0, 1, 2, 3, 4 and 5 in yellow, the Pro-Ala-rich
linker in blue, and the site of mutations in C1 as a light green
patch on C1. The MyBP-C motif between C1 and C2 is shown to have
three phosphorylation sites (3P). It is envisaged that the
binding of C0 and the AB Motif may occur in resting muscle but
will be labile and easily broken.
|
