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PDBsum entry 1tnn
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Muscle protein
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PDB id
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1tnn
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Contents |
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* Residue conservation analysis
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Enzyme class:
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E.C.2.7.11.1
- non-specific serine/threonine protein kinase.
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Reaction:
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1.
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L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + H+
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2.
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L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] + ADP + H+
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L-seryl-[protein]
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+
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ATP
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=
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O-phospho-L-seryl-[protein]
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+
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ADP
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+
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H(+)
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L-threonyl-[protein]
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+
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ATP
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=
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O-phospho-L-threonyl-[protein]
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+
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ADP
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+
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H(+)
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Molecule diagrams generated from .mol files obtained from the
KEGG ftp site
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DOI no:
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Structure
3:391-401
(1995)
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PubMed id:
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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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M.Pfuhl,
A.Pastore.
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ABSTRACT
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BACKGROUND: Titin is a gigantic protein located in the thick filament of
vertebrate muscles. The putative functions of titin range from interactions with
myosin and other muscle proteins to a role in muscle recoil. Analysis of its
complete sequence has shown that titin is a multi-domain protein containing
several copies of modules of 100 amino acids each. These are thought to belong
to the fibronectin type-III and immunoglobulin superfamilies. So far, a complete
structural determination has not been carried out on any of the titin modules.
RESULTS: The three-dimensional structure of an immunoglobulin module, located in
the M-line of the sarcomere close to the titin C terminus and called 'M5', was
determined by multi-dimensional NMR spectroscopy. The structure has the
predicted immunoglobulin fold with two beta-sheets packed against each other.
Each sheet contains four strands. The structure of M5 belongs to the I
(intermediate) set of the immunoglobulin superfamily and is very similar to
telokin, which is also found in muscles. Although M5 and telokin have relatively
little sequence similarity, the two proteins clearly share the same hydrophobic
core. The major difference between telokin and the titin M5 module is the
absence of the C' strand in the latter. CONCLUSIONS: The titin domains and
several of the immunoglobulin-like domains from other modular muscle proteins
are highly conserved at the positions corresponding to the hydrophobic core of
M5. Our results indicate that it may be possible to use the structure of M5 as a
molecular template to model most of the other immunoglobulin-like domains in
muscle titin.
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Selected figure(s)
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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
reprinted
by permission from Cell Press:
Structure
(1995,
3,
391-401)
copyright 1995.
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Figures were
selected
by an automated process.
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Literature references that cite this PDB file's key reference
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PubMed id
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Reference
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A.Kontrogianni-Konstantopoulos,
M.A.Ackermann,
A.L.Bowman,
S.V.Yap,
and
R.J.Bloch
(2009).
Muscle giants: molecular scaffolds in sarcomerogenesis.
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Physiol Rev,
89,
1217-1267.
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C.A.Otey,
R.Dixon,
C.Stack,
and
S.M.Goicoechea
(2009).
Cytoplasmic Ig-domain proteins: cytoskeletal regulators with a role in human disease.
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Cell Motil Cytoskeleton,
66,
618-634.
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J.Kopecek,
and
J.Yang
(2009).
Peptide-directed self-assembly of hydrogels.
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Acta Biomater,
5,
805-816.
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M.M.Balamurali,
D.Sharma,
A.Chang,
D.Khor,
R.Chu,
and
H.Li
(2008).
Recombination of protein fragments: a promising approach toward engineering proteins with novel nanomechanical properties.
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Protein Sci,
17,
1815-1826.
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A.Ababou,
M.Gautel,
and
M.Pfuhl
(2007).
Dissecting the N-terminal myosin binding site of human cardiac myosin-binding protein C. Structure and myosin binding of domain C2.
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J Biol Chem,
282,
9204-9215.
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PDB code:
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M.Marino,
D.I.Svergun,
L.Kreplak,
P.V.Konarev,
B.Maco,
D.Labeit,
and
O.Mayans
(2005).
Poly-Ig tandems from I-band titin share extended domain arrangements irrespective of the distinct features of their modular constituents.
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J Muscle Res Cell Motil,
26,
355-365.
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L.Tskhovrebova,
and
J.Trinick
(2004).
Properties of titin immunoglobulin and fibronectin-3 domains.
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J Biol Chem,
279,
46351-46354.
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M.Cieplak,
T.X.Hoang,
and
M.O.Robbins
(2004).
Thermal effects in stretching of Go-like models of titin and secondary structures.
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Proteins,
56,
285-297.
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L.Tskhovrebova,
and
J.Trinick
(2003).
Titin: properties and family relationships.
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Nat Rev Mol Cell Biol,
4,
679-689.
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R.A.George,
and
J.Heringa
(2002).
Protein domain identification and improved sequence similarity searching using PSI-BLAST.
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Proteins,
48,
672-681.
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O.Mayans,
J.Wuerges,
S.Canela,
M.Gautel,
and
M.Wilmanns
(2001).
Structural evidence for a possible role of reversible disulphide bridge formation in the elasticity of the muscle protein titin.
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Structure,
9,
331-340.
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PDB code:
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P.Young,
E.Ehler,
and
M.Gautel
(2001).
Obscurin, a giant sarcomeric Rho guanine nucleotide exchange factor protein involved in sarcomere assembly.
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J Cell Biol,
154,
123-136.
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R.B.Best,
B.Li,
A.Steward,
V.Daggett,
and
J.Clarke
(2001).
Can non-mechanical proteins withstand force? Stretching barnase by atomic force microscopy and molecular dynamics simulation.
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Biophys J,
81,
2344-2356.
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E.Paci,
and
M.Karplus
(2000).
Unfolding proteins by external forces and temperature: the importance of topology and energetics.
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Proc Natl Acad Sci U S A,
97,
6521-6526.
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R.A.Atkinson,
C.Joseph,
F.Dal Piaz,
L.Birolo,
G.Stier,
P.Pucci,
and
A.Pastore
(2000).
Binding of alpha-actinin to titin: implications for Z-disk assembly.
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Biochemistry,
39,
5255-5264.
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B.Kolmerer,
C.C.Witt,
A.Freiburg,
S.Millevoi,
G.Stier,
H.Sorimachi,
K.Pelin,
L.Carrier,
K.Schwartz,
D.Labeit,
C.C.Gregorio,
W.A.Linke,
and
S.Labeit
(1999).
The titin cDNA sequence and partial genomic sequences: insights into the molecular genetics, cell biology and physiology of the titin filament system.
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Rev Physiol Biochem Pharmacol,
138,
19-55.
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F.E.Somnier,
G.O.Skeie,
J.A.Aarli,
and
W.Trojaborg
(1999).
EMG evidence of myopathy and the occurrence of titin autoantibodies in patients with myasthenia gravis.
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Eur J Neurol,
6,
555-563.
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G.M.Benian,
A.Ayme-Southgate,
and
T.L.Tinley
(1999).
The genetics and molecular biology of the titin/connectin-like proteins of invertebrates.
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Rev Physiol Biochem Pharmacol,
138,
235-268.
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C.M.Goll,
A.Pastore,
and
M.Nilges
(1998).
The three-dimensional structure of a type I module from titin: a prototype of intracellular fibronectin type III domains.
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Structure,
6,
1291-1302.
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PDB code:
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H.Lu,
B.Isralewitz,
A.Krammer,
V.Vogel,
and
K.Schulten
(1998).
Unfolding of titin immunoglobulin domains by steered molecular dynamics simulation.
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Biophys J,
75,
662-671.
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R.Urfer,
P.Tsoulfas,
L.O'Connell,
J.A.Hongo,
W.Zhao,
and
L.G.Presta
(1998).
High resolution mapping of the binding site of TrkA for nerve growth factor and TrkC for neurotrophin-3 on the second immunoglobulin-like domain of the Trk receptors.
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J Biol Chem,
273,
5829-5840.
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S.J.Hamill,
A.E.Meekhof,
and
J.Clarke
(1998).
The effect of boundary selection on the stability and folding of the third fibronectin type III domain from human tenascin.
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Biochemistry,
37,
8071-8079.
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C.Chothia,
and
E.Y.Jones
(1997).
The molecular structure of cell adhesion molecules.
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Annu Rev Biochem,
66,
823-862.
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D.J.Leahy
(1997).
Implications of atomic-resolution structures for cell adhesion.
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Annu Rev Cell Dev Biol,
13,
363-393.
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A.Bateman,
M.Jouet,
J.MacFarlane,
J.S.Du,
S.Kenwrick,
and
C.Chothia
(1996).
Outline structure of the human L1 cell adhesion molecule and the sites where mutations cause neurological disorders.
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EMBO J,
15,
6050-6059.
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A.Bateman,
S.R.Eddy,
and
C.Chothia
(1996).
Members of the immunoglobulin superfamily in bacteria.
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Protein Sci,
5,
1939-1941.
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A.Freiburg,
and
M.Gautel
(1996).
A molecular map of the interactions between titin and myosin-binding protein C. Implications for sarcomeric assembly in familial hypertrophic cardiomyopathy.
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Eur J Biochem,
235,
317-323.
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B.Kobe,
J.Heierhorst,
S.C.Feil,
M.W.Parker,
G.M.Benian,
K.R.Weiss,
and
B.E.Kemp
(1996).
Giant protein kinases: domain interactions and structural basis of autoregulation.
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EMBO J,
15,
6810-6821.
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PDB codes:
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M.Gautel,
E.Lehtonen,
and
F.Pietruschka
(1996).
Assembly of the cardiac I-band region of titin/connectin: expression of the cardiac-specific regions and their structural relation to the elastic segments.
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J Muscle Res Cell Motil,
17,
449-461.
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N.K.Thomsen,
V.Soroka,
P.H.Jensen,
V.Berezin,
V.V.Kiselyov,
E.Bock,
and
F.M.Poulsen
(1996).
The three-dimensional structure of the first domain of neural cell adhesion molecule.
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Nat Struct Biol,
3,
581-585.
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PDB codes:
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S.Improta,
A.S.Politou,
and
A.Pastore
(1996).
Immunoglobulin-like modules from titin I-band: extensible components of muscle elasticity.
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Structure,
4,
323-337.
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PDB codes:
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W.M.Obermann,
M.Gautel,
F.Steiner,
P.F.van der Ven,
K.Weber,
and
D.O.Fürst
(1996).
The structure of the sarcomeric M band: localization of defined domains of myomesin, M-protein, and the 250-kD carboxy-terminal region of titin by immunoelectron microscopy.
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J Cell Biol,
134,
1441-1453.
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A.Bateman,
and
C.Chothia
(1995).
Outline structures for the extracellular domains of the fibroblast growth factor receptors.
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Nat Struct Biol,
2,
1068-1074.
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A.S.Politou,
D.J.Thomas,
and
A.Pastore
(1995).
The folding and stability of titin immunoglobulin-like modules, with implications for the mechanism of elasticity.
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Biophys J,
69,
2601-2610.
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The most recent references are shown first.
Citation data come partly from CiteXplore and partly
from an automated harvesting procedure. Note that this is likely to be
only a partial list as not all journals are covered by
either method. However, we are continually building up the citation data
so more and more references will be included with time.
Where a reference describes a PDB structure, the PDB
code is
shown on the right.
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Links
