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PDBsum entry 2bl0
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Muscle protein
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PDB id
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2bl0
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Contents |
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63 a.a.
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145 a.a.
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142 a.a.
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References listed in PDB file
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Key reference
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Title
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Structural evidence for non-Canonical binding of ca2+ to a canonical ef-Hand of a conventional myosin.
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Authors
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J.E.Debreczeni,
L.Farkas,
V.Harmat,
C.Hetényi,
I.Hajdú,
P.Závodszky,
K.Kohama,
L.Nyitray.
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Ref.
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J Biol Chem, 2005,
280,
41458-41464.
[DOI no: ]
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PubMed id
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Abstract
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We have previously identified a single inhibitory Ca2+-binding site in the first
EF-hand of the essential light chain of Physarum conventional myosin (Farkas,
L., Malnasi-Csizmadia, A., Nakamura, A., Kohama, K., and Nyitray, L. (2003) J.
Biol. Chem. 278, 27399-27405). As a general rule, conformation of the
EF-hand-containing domains in the calmodulin family is "closed" in the
absence and "open" in the presence of bound cations; a notable
exception is the unusual Ca2+-bound closed domain in the essential light chain
of the Ca2+-activated scallop muscle myosin. Here we have reported the 1.8 A
resolution structure of the regulatory domain (RD) of Physarum myosin II in
which Ca2+ is bound to a canonical EF-hand that is also in a closed state. The
12th position of the EF-hand loop, which normally provides a bidentate ligand
for Ca2+ in the open state, is too far in the structure to participate in
coordination of the ion. The structure includes a second Ca2+ that only mediates
crystal contacts. To reveal the mechanism behind the regulatory effect of Ca2+,
we compared conformational flexibilities of the liganded and unliganded RD. Our
working hypothesis, i.e. the modulatory effect of Ca2+ on conformational
flexibility of RD, is in line with the observed suppression of
hydrogen-deuterium exchange rate in the Ca2+-bound form, as well as with results
of molecular dynamics calculations. Based on this evidence, we concluded that
Ca2+-induced change in structural dynamics of RD is a major factor in
Ca2+-mediated regulation of Physarum myosin II activity.
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Figure 2.
FIGURE 2. Structure and comparison of the Ca^2+ binding
EF-hands of ELC and CaM. A, octahedral coordination of Ca^2+ ion
in the first EF-hand of ELC showing an unusual closed
conformation. Ca^2+ is coordinated by Asp-15, Asp-17, Asp-19,
Lys-21, and two water molecules (red dots). Glu-26, which
normally provides a bidentate ligand for Ca^2+ in the open
state, is too far in the structure to participate in
coordination of the ion. B, comparison of the Ca^2+ binding
EF-hand I of the Physarum (red) and scallop myosins (blue;
Protein Data Bank accession code 1wdc) and the mutant CaM
structure (green; 1y6w) reveals high similarity between the
Physarum and the mutant CaM structure. Note the extra turn in
the first helix of scallop ELC. r.m.s. deviations of the
backbone carbons, after superimposing the scallop and calmodulin
structures, are 0.53 Å.
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Figure 4.
FIGURE 4. Conformation of the heavy chain in the Physarum,
scallop muscle and chicken skeletal muscle myosin RD,
respectively. A least squares superposition of the long helical
neck region from the Physarum (gray), scallop (blue; Protein
Data Bank accession code 1wdc), and chicken (yellow; 2mys)
myosins is shown. The Physarum RD shows the sharpest bend at the
hook region (RLC interlobe interface) and the smallest bend at
the ELC-RLC interface.
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The above figures are
reprinted
by permission from the ASBMB:
J Biol Chem
(2005,
280,
41458-41464)
copyright 2005.
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