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Figure 1.
Fig. 1. (a) Schematic representation of the 11 domains [8
immunoglobulin (Ig) and 3 fibronectin (Fn)] of cardiac MyBP-C.
(b) Amino acid residues 1–258 of the N-terminal region C0C1 of
cMyBP-C derived from the pET-28a vector DNA, including the
hexahistidine tag and a thrombin cleavage site (LVPRGS). The
sequence highlighted in orange shows the residues seen in
crystals of the C1 structure with the sequence in the Pro-Ala
linker disordered. (c) Illustration of the key known HCM
mutations in the N-terminal domains C0, C1 and C2 of human
cMyBP-C. Also shown is the C1–C2 linker with the LAGGGRRIS
insertion that can be phosphorylated (shown in pink) and is
reported to bind to myosin S2.^5 (d) Multiple sequence alignment
of the C1 domain of MyBP-C from different species. Arrows show
key HCM mutation sites D228N, Y237S, H257P and E258K. Sequence
alignments were produced using CLUSTALW [www.ebi.ac.uk/clustalw]
and displayed using the Jalview alignment editor.^6 (e) Sequence
alignment of the N-terminal extension on the ELC of human atrial
myosin and the C-terminal end of the cMyBP-C C0 domain together
with the Pro-Ala linker between C0 and C1 that follows. The
boxed sequences, rich in lysines (blue), are thought to form an
actin binding site.^7 Acidic residues are shown in red.
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