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PDBsum entry 2ec6
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Contractile protein
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PDB id
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2ec6
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Contents |
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802 a.a.
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126 a.a.
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155 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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Rigor-Like structures from muscle myosins reveal key mechanical elements in the transduction pathways of this allosteric motor.
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Authors
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Y.Yang,
S.Gourinath,
M.Kovács,
L.Nyitray,
R.Reutzel,
D.M.Himmel,
E.O'Neall-Hennessey,
L.Reshetnikova,
A.G.Szent-Györgyi,
J.H.Brown,
C.Cohen.
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Ref.
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Structure, 2007,
15,
553-564.
[DOI no: ]
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PubMed id
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Abstract
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Unlike processive cellular motors such as myosin V, whose structure has recently
been determined in a "rigor-like" conformation, myosin II from
contracting muscle filaments necessarily spends most of its time detached from
actin. By using squid and sea scallop sources, however, we have now obtained
similar rigor-like atomic structures for muscle myosin heads (S1). The
significance of the hallmark closed actin-binding cleft in these crystal
structures is supported here by actin/S1-binding studies. These structures
reveal how different duty ratios, and hence cellular functions, of the myosin
isoforms may be accounted for, in part, on the basis of detailed differences in
interdomain contacts. Moreover, the rigor-like position of switch II turns out
to be unique for myosin V. The overall arrangements of subdomains in the motor
are relatively conserved in each of the known contractile states, and we explore
qualitatively the energetics of these states.
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Figure 2.
Figure 2. Comparison of the Rigor-like and Post-Rigor States
of Muscle Myosin S1 and Its Active Site
(A and B) Detailed
legends for all figures are supplied in Supplemental Data. (A)
Schematic overlay of (squid) S1 in the two states (see text).
The rigor-like state is shown in green, and the post-rigor state
is shown in red. Thicker lines indicate proximity to the reader.
The overall conformational differences between these (and the
pre-power stroke) states are generally conserved in the
different isoforms. The locations of interdomain interactions
that nevertheless appear to preferentially stabilize the
high-duty ratio non-muscle myosin V in a rigor-like conformation
and some of the low-duty ratio myosin II isoforms in a
non-rigor-like (actin-detached) conformation are indicated here
with blue and red asterisks, respectively (also see text and
Figure 3, Figure 4 and Figure 5). (B) The rigor-like location of
switch II in the various myosin II and VI structures (green),
which have small side chains at (squid) position 465, differs
from that in myosin V (blue), in which 465 is a tyrosine. The
locations of both switch I and switch II away from the
nucleotide and near each other force the tyrosine to adopt a
“g−” rotamer. The myosin V switch II is displaced toward
the P loop of the N-terminal subdomain in the rigor-like state
to avoid a clash of this rotamer with helix W (not shown). In
the post-rigor state (red), switch I (including Ser246) is near
the nucleotide and relatively far from switch II. Here, the
tyrosine has room to adopt the “g+” rotamer and does not
perturb the arrangement of the active site elements.
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Figure 3.
Figure 3. Conserved and Variable Features of the Rigor-like
50 kDa Cleft
(A–E) The schematic S1 inset on this and
subsequent figures shows the region that is magnified (box) and
the viewpoint (arrow). Squid sequence numbering is used. (A)
Displayed are selected interactions between the upper (dark
green) and lower (light green) 50 kDa subdomains made in the
squid rigor-like structure that are also made (with identical or
homologous residues) in the other isoforms studied when the
corresponding part of their cleft is also fully closed.
Interactions include H-bonded/electrostatic contacts (dotted
lines) and extensive burial of certain apolar residues
(underlined labels). (B–E) Variations in crosscleft contacts,
as well as in the orientations of the upper and lower 50 kDa
subdomains or of subregions within them, help determine the
extent of inner and outer cleft closure in the various isoforms
(the green, dashed line shows squid for comparison.) (B) Myosin
V displays the most closed cleft in the strut region (also see
Table 1), perhaps due to a “complex H-bond link” (blue,
dotted lines) between Asn424, Lys601, and Glu598 not seen in any
other isoform; position 598 is aspartate in squid and sea
scallop, and 424 is serine in Dictyostelium (see below for
myosin VI). (C) A slightly modified orientation of helix HR
relative to helix HQ yields a fully closed outer but
incompletely closed inner cleft in catch and striated sea
scallop S1. (D) Curvature of helix HO about a
Dictyostelium-specific glycine at 435 contributes to its fully
closed inner but partially open outer cleft. (E) The entire
cleft of myosin VI is incompletely closed. A myosin VI-specific
lysine at position 650 appears to disrupt the interdomain
602-274-431 complex salt link made from the strut.
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The above figures are
reprinted
by permission from Cell Press:
Structure
(2007,
15,
553-564)
copyright 2007.
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