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PDBsum entry 1kql
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Contractile protein
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PDB id
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1kql
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Contents |
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* Residue conservation analysis
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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 crystal structure of the c-Terminal fragment of striated-Muscle alpha-Tropomyosin reveals a key troponin t recognition site.
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Authors
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Y.Li,
S.Mui,
J.H.Brown,
J.Strand,
L.Reshetnikova,
L.S.Tobacman,
C.Cohen.
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Ref.
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Proc Natl Acad Sci U S A, 2002,
99,
7378-7383.
[DOI no: ]
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PubMed id
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Abstract
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Contraction in striated and cardiac muscles is regulated by the motions of a
Ca(2+)-sensitive tropomyosin/troponin switch. In contrast, troponin is absent in
other muscle types and in nonmuscle cells, and actomyosin regulation is
myosin-linked. Here we report an unusual crystal structure at 2.7 A of the
C-terminal 31 residues of rat striated-muscle alpha-tropomyosin (preceded by a
fragment of the GCN4 leucine zipper). The C-terminal 22 residues (263-284) of
the structure do not form a two-stranded alpha-helical coiled coil as does the
rest of the molecule, but here the alpha-helices splay apart and are stabilized
by the formation of a tail-to-tail dimer with a symmetry-related molecule. The
site of splaying involves a small group of destabilizing core residues that is
present only in striated muscle tropomyosin isoforms. These results reveal a
specific recognition site for troponin T and clarify the physical basis for the
unique regulatory mechanism of striated muscles.
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Figure 2.
Fig. 2. Structural basis for the splaying in the
C-terminal region of striated muscle Tm. (A) In the C-terminal
region of striated muscle  -Tm, there
are three consecutive "core" residues (blue) that are generally
disfavored in two-stranded coiled coils: Gln-263 (d position),
Tyr-267 (a position), and Ile-270 (d position). The two
equivalent Ile side chains do not contact each other, and the
pairs of Gln and Tyr side chains do not display the usual
symmetric "knobs-into-holes" packing pattern. In each of these
two cases (B and C), only one of the two equivalent residues is
inserted into the hole on the opposite helix. Moreover, the
distance between the two helices increases to accommodate the
insertion of such long or bulky side chains.
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Figure 3.
Fig. 3. Structural variations in the C-terminal region of
different vertebrate Tm isoforms. (A) Coiled-coil predictions,
using the program COILS (28-29) (with a 14-residue window size)
for the C-terminal regions of the products of the -Tm gene.
In striated-muscle -Tm,
encoded by exon 9a (red squares), the coiled-coil propensity
decreases sharply after Gln-263, consistent with a 22-residue
splayed region observed in the current study (see Materials and
Methods). Vertebrate smooth-muscle -Tm and
many nonmuscle isoforms, encoded by exon 9d (green circles), are
also predicted to be -helical
but not in a two-stranded coiled-coil conformation at the C
terminus. However, the coiled coil in these isoforms appears to
extend beyond residue 262 to at least residue 270. In the brain
isoforms, TmBr-1 and TmBr-3, encoded by exon 9c (dotted line),
the C terminus is predicted to be an -helical
coiled coil to the very end. In another brain isoform, TmBr-2,
encoded by exon 9b (solid line), the C-terminal region is mostly
likely not -helical
because of three closely spaced prolines. (B) Schematic
representation of the C-terminal ends of striated- and
smooth-muscle -Tms.
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