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PDBsum entry 3jvt
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Contractile protein
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PDB id
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3jvt
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Contents |
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63 a.a.
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156 a.a.
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156 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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The on-Off switch in regulated myosins: different triggers but related mechanisms.
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Authors
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D.M.Himmel,
S.Mui,
E.O'Neall-Hennessey,
A.G.Szent-Györgyi,
C.Cohen.
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Ref.
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J Mol Biol, 2009,
394,
496-505.
[DOI no: ]
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PubMed id
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Abstract
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In regulated myosin, motor and enzymatic activities are toggled between the
on-state and off-state by a switch located on its lever arm domain, here called
the regulatory domain (RD). This region consists of a long alpha-helical "heavy
chain" stabilized by a "regulatory" light chain (RLC) and an "essential" light
chain (ELC). The on-state is activated by phosphorylation of the RLC of
vertebrate smooth muscle RD or by direct binding of Ca(2+) to the ELC of
molluscan RD. Crystal structures are available only for the molluscan RD. To
understand in more detail the pathway between the on-state and the off-state, we
have now also determined the crystal structure of a molluscan (scallop) RD in
the absence of Ca(2+). Our results indicate that loss of Ca(2+) abolishes most
of the interactions between the light chains and may increase the flexibility of
the RD heavy chain. We propose that disruption of critical links with the C-lobe
of the RLC is the key event initiating the off-state in both smooth muscle
myosins and molluscan myosins.
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Figure 3.
Fig. 3. Ca^2+ binding stabilizesHC/RLC/ELC interactions in
scallop structures. (a) Shown is a vast hydrogen-bond and
covalent-bond network in the Ca^2+-RD structure extending from
the Ca^2+ binding site to Lys149 on the RLC N-lobe. (b) Part of
this network forms a meshwork that stabilizes the coordination
of Ca^2+, shown here schematically. Solid gray lines indicate
main-chain interactions, and wavy lines indicate side-chain
interactions. (c) The same meshwork as (b) in the absence of
Ca^2+. Notice that when the Gly23 carbonyl rotates away from the
Ca^2+ binding site, four hydrogen bonds from this meshwork are
abolished.
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Figure 5.
Fig. 5. Scallop and squid RLC. Scallop (color) and squid
(gray tones; PDB code 2OVK)^30 are superposed (superposition
based on scallop HC residues 807–818 and equivalent squid HC
residues 809–820). The scallop structure is shown oriented as
in Fig. 4. In the squid crystal structure, the RLC N-lobe is
rotated closer to the C-lobe, bringing helix A and the RLC
N-terminus within reach of helices E and H. RLC residue C^α
distances are shown (in Å) for scallop Asp84-Lys149
(magenta), scallop Pro13-Asp84 (tan), and squid Arg13-Glu84
(black).
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The above figures are
reprinted
by permission from Elsevier:
J Mol Biol
(2009,
394,
496-505)
copyright 2009.
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Secondary reference #1
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Title
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Structure of the regulatory domain of scallop myosin at 2 a resolution: implications for regulation.
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Authors
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A.Houdusse,
C.Cohen.
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Ref.
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structure, 1996,
4,
21.
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Secondary reference #2
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Title
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Structure of the regulatory domain of scallop myosin at 2.8 a resolution.
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Authors
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X.Xie,
D.H.Harrison,
I.Schlichting,
R.M.Sweet,
V.N.Kalabokis,
A.Szent-Gyorgyi,
C.Cohen.
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Ref.
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nature, 1994,
368,
306.
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