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PDBsum entry 1nct
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Muscle protein
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PDB id
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1nct
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References listed in PDB file
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Key reference
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Title
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When a module is also a domain: the rôle of the n terminus in the stability and the dynamics of immunoglobulin domains from titin.
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Authors
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M.Pfuhl,
S.Improta,
A.S.Politou,
A.Pastore.
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Ref.
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J Mol Biol, 1997,
265,
242-256.
[DOI no: ]
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PubMed id
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Note In the PDB file this reference is
annotated as "TO BE PUBLISHED".
The citation details given above were identified by an automated
search of PubMed on title and author
names, giving a
percentage match of
83%.
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Abstract
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In the course of a structural study of titin, a giant modular protein from
muscle, we have reported that N-terminal extension of immunoglobulin-like
(Ig-like) domains from titin stabilizes this fold. In order to investigate the
structural basis of such an effect, we have solved the structure of NEXTM5,
which has six amino acids added to the sequence of M5, a domain for which full
structure determination has been previously achieved. In the present work, the
structures and the dynamics of M5 and NEXTM5 are compared in the light of data
collected for these and other titin domains. In NEXTM5, three out of the six
added residues are structured and pack against the nearby BC and FG loops. As a
consequence, three new backbone hydrogen bonds are formed with the B strand,
extending the A strand by two residues and decreasing the exposed surface area
of the loops. Additional contacts which involve the side-chains give rise to a
remarkable pH dependence of the stability. Interestingly, no correlation is
observed on the NMR time-scale between the overall dynamics of the extended
domain and its increased stability. The most noticeable differences between the
two constructs are localised around the N terminus, which becomes more rigid
upon extension. Since a similar pattern of contacts is observed for other
domains of the immunoglobulin I-set, our results are of general relevance for
this protein family. Our work might also inspire a more rational approach to the
investigation of domain boundaries and their influence on module stability.
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Figure 2.
Figure 2. Difference of the NEXTM5 − M5 chemical shifts
of α (broken line) and amide protons (continuous line).
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Figure 8.
Figure 8. Pattern of hydrogen bonds for the β-sheet
containing the N terminus in M5 (A), telokin (B) and I27 (C)
with the relative variation of stability observed in M5 and I27
indicated below. The residues added upon extension of I27 and M5
are indicated in grey. The additional H-bonds formed in the two
domains are indicated with broken lines. The melting point
(t[m]) and the midpoint urea concentration ([U][1/2]) are
expressed in deg.C and mol/l, respectively. The construct names
are chosen to be consistent with previous publications.
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The above figures are
reprinted
by permission from Elsevier:
J Mol Biol
(1997,
265,
242-256)
copyright 1997.
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Secondary reference #1
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Title
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Immunoglobulin-Like modules from titin i-Band: extensible components of muscle elasticity.
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Authors
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S.Improta,
A.S.Politou,
A.Pastore.
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Ref.
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Structure, 1996,
4,
323-337.
[DOI no: ]
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PubMed id
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Figure 7.
Figure 7. Comparison of the four structures so far
determined which belong to the I frame of the immunoglobulin
superfamily. They are titin I27 (magenta), titin M5 (cyan),
telokin (blue) and the N-terminal domain of VCAM (green). A
MOLSCRIPT representation and the same orientation are used.
Figure 7. Comparison of the four structures so far
determined which belong to the I frame of the immunoglobulin
superfamily. They are titin I27 (magenta), titin M5 (cyan),
telokin (blue) and the N-terminal domain of VCAM (green). A
MOLSCRIPT representation and the same orientation are used.
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Figure 10.
Figure 10. Model of an I27–I28 module pair. It represents the
smallest unit containing the Ig–Ig interface observed only in
the titin I-band region. I27 and I28 are respectively indicated
in magenta and purple to match the colours used in Figure 1b.
The linker region between the two modules is indicated in white
and it is shown in its extended form. Figure 10. Model of an
I27–I28 module pair. It represents the smallest unit
containing the Ig–Ig interface observed only in the titin
I-band region. I27 and I28 are respectively indicated in magenta
and purple to match the colours used in [3]Figure 1b. The linker
region between the two modules is indicated in white and it is
shown in its extended form.
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The above figures are
reproduced from the cited reference
with permission from Cell Press
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Secondary reference #2
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Title
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Tertiary structure of an immunoglobulin-Like domain from the giant muscle protein titin: a new member of the i set.
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Authors
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M.Pfuhl,
A.Pastore.
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Ref.
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Structure, 1995,
3,
391-401.
[DOI no: ]
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PubMed id
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Figure 7.
Figure 7. Part of the hydrophobic core of M5. A hydrogen bond
is formed between the Tyr70 hydroxyl proton and the backbone
carbonyls of Asp66 and Glu67. The aromatic ring packs against
Leu40. The side chain carboxylate group of Asp66 forms ion
bridges with His46 and weakly with Arg45. Hydrogen bonds/ionic
interactions are indicated by dashed lines. Figure 7. Part of
the hydrophobic core of M5. A hydrogen bond is formed between
the Tyr70 hydroxyl proton and the backbone carbonyls of Asp66
and Glu67. The aromatic ring packs against Leu40. The side chain
carboxylate group of Asp66 forms ion bridges with His46 and
weakly with Arg45. Hydrogen bonds/ionic interactions are
indicated by dashed lines.
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Figure 8.
Figure 8. (a) Interaction of Tyr53 with the loop around
Pro27-Pro29. The aromatic ring of Tyr53 packs against the
hydrophobic surface provided by Pro27, Val28 and Pro29. The two
prolines are in cis and trans conformations, respectively. A
hydrogen bond is formed from the hydroxyl proton of Tyr53 to the
side chain carboxylate of Asp24.(b) Alternative interactions of
Asp24 with Arg1 in the family of 16 accepted structures. Side
chains of Arg1, Asp24 and Tyr53 are shown for the 16 best
structures while the backbone is only shown for the average
structure. Figure 8. (a) Interaction of Tyr53 with the loop
around Pro27-Pro29. The aromatic ring of Tyr53 packs against the
hydrophobic surface provided by Pro27, Val28 and Pro29. The two
prolines are in cis and trans conformations, respectively. A
hydrogen bond is formed from the hydroxyl proton of Tyr53 to the
side chain carboxylate of Asp24. (b) Alternative interactions of
Asp24 with Arg1 in the family of 16 accepted structures. Side
chains of Arg1, Asp24 and Tyr53 are shown for the 16 best
structures while the backbone is only shown for the average
structure.
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The above figures are
reproduced from the cited reference
with permission from Cell Press
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Secondary reference #3
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Title
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Secondary structure determination by nmr spectroscopy of an immunoglobulin-Like domain from the giant muscle protein titin.
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Authors
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M.Pfuhl,
M.Gautel,
A.S.Politou,
C.Joseph,
A.Pastore.
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Ref.
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J Biomol Nmr, 1995,
6,
48-58.
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PubMed id
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Secondary reference #4
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Title
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Immunoglobulin-Type domains of titin are stabilized by amino-Terminal extension.
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Authors
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A.S.Politou,
M.Gautel,
C.Joseph,
A.Pastore.
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Ref.
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FEBS Lett, 1994,
352,
27-31.
[DOI no: ]
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PubMed id
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