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PDBsum entry 1ya5

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protein ligands Protein-protein interface(s) links
Structural protein PDB id
1ya5
Jmol
Contents
Protein chains
198 a.a. *
89 a.a. *
Ligands
SO4 ×5
Waters ×179
* Residue conservation analysis
PDB id:
1ya5
Name: Structural protein
Title: Crystal structure of the titin domains z1z2 in complex with
Structure: N2b-titin isoform. Chain: a, b. Fragment: domains z1z2, residues 1-196. Synonym: ttn protein. Titin isoform novex-2. Titin isoform engineered: yes. Telethonin. Chain: t. Fragment: residues 1-90. Synonym: titin cap protein.
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562.
Biol. unit: Trimer (from PQS)
Resolution:
2.44Å     R-factor:   0.233     R-free:   0.265
Authors: N.Pinotsis,A.Popov,P.Zou,M.Wilmanns
Key ref:
P.Zou et al. (2006). Palindromic assembly of the giant muscle protein titin in the sarcomeric Z-disk. Nature, 439, 229-233. PubMed id: 16407954 DOI: 10.1038/nature04343
Date:
17-Dec-04     Release date:   20-Dec-05    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
Q8WZ42  (TITIN_HUMAN) -  Titin
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34350 a.a.
198 a.a.*
Protein chain
Pfam   ArchSchema ?
O15273  (TELT_HUMAN) -  Telethonin
Seq:
Struc:
167 a.a.
89 a.a.*
Key:    PfamA domain  PfamB domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 6 residue positions (black crosses)

 Enzyme reactions 
   Enzyme class: Chains A, B: E.C.2.7.11.1  - Non-specific serine/threonine protein kinase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: ATP + a protein = ADP + a phosphoprotein
ATP
+ protein
= ADP
+ phosphoprotein
Molecule diagrams generated from .mol files obtained from the KEGG ftp site

 

 
    reference    
 
 
DOI no: 10.1038/nature04343 Nature 439:229-233 (2006)
PubMed id: 16407954  
 
 
Palindromic assembly of the giant muscle protein titin in the sarcomeric Z-disk.
P.Zou, N.Pinotsis, S.Lange, Y.H.Song, A.Popov, I.Mavridis, O.M.Mayans, M.Gautel, M.Wilmanns.
 
  ABSTRACT  
 
The Z-disk of striated and cardiac muscle sarcomeres is one of the most densely packed cellular structures in eukaryotic cells. It provides the architectural framework for assembling and anchoring the largest known muscle filament systems by an extensive network of protein-protein interactions, requiring an extraordinary level of mechanical stability. Here we show, using X-ray crystallography, how the amino terminus of the longest filament component, the giant muscle protein titin, is assembled into an antiparallel (2:1) sandwich complex by the Z-disk ligand telethonin. The pseudosymmetric structure of telethonin mediates a unique palindromic arrangement of two titin filaments, a type of molecular assembly previously found only in protein-DNA complexes. We have confirmed its unique architecture in vivo by protein complementation assays, and in vitro by experiments using fluorescence resonance energy transfer. The model proposed may provide a molecular paradigm of how major sarcomeric filaments are crosslinked, anchored and aligned within complex cytoskeletal networks.
 
  Selected figure(s)  
 
Figure 1.
Figure 1: Structure of the palindromic titin-telethonin-titin complex. Colour codes: blue, titin immunoglobulin-like domain Z1 (residues 1-98); cyan, titin immunoglobulin-like domain Z2, including the Z1-Z2 linker (99-196); red, telethonin(1-59); green, telethonin(60-90). a, Ribbon representation. b, Schematic representation of the -sheet structure in the titin-telethonin (2:1) complex. Arg 87 of telethonin, which is linked to dilated cardiomyopathy, is coloured yellow10. The -sheet hydrogen bonds are depicted by lines. For clarity, only those parts of the two immunoglobulin-like tandem repeats from titin that are involved in interactions with telethonin are shown. c, Surface presentation of the titin-telethonin-titin complex in two orientations, rotated by 180° relative to each other.
Figure 4.
Figure 4: Model outlining the involvement of the titin-telethonin complex in the architecture of the sarcomeric Z-disk. Titin filaments are assembled by a dual Z-disk bridging system, by -actinin rods on a variable number of titin Z-repeats (three bridges are shown), and by telethonin by means of the N-terminal immunoglobulin domains Z1 and Z2. The titin N-terminus/telethonin complex forms a core that interacts with several ligands both inside and outside the sarcomeric Z-disk, including MLP, sAnkyrin, the -subunit of the potassium channel (minK) and the -filamin/ABP-L, -actinin and telethonin binding protein of the Z-disc (FATZ).
 
  The above figures are reprinted by permission from Macmillan Publishers Ltd: Nature (2006, 439, 229-233) copyright 2006.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21332356 J.Hsin, J.Strümpfer, E.H.Lee, and K.Schulten (2011).
Molecular origin of the hierarchical elasticity of titin: simulation, experiment, and theory.
  Annu Rev Biophys, 40, 187-203.  
21555460 K.da Silva Lopes, A.Pietas, M.H.Radke, and M.Gotthardt (2011).
Titin visualization in real time reveals an unexpected level of mobility within and between sarcomeres.
  J Cell Biol, 193, 785-798.  
21190822 M.Gautel (2011).
The sarcomeric cytoskeleton: who picks up the strain?
  Curr Opin Cell Biol, 23, 39-46.  
19488834 H.Cheng, X.Xu, S.Zhao, B.Liu, M.Yu, and B.Fan (2010).
Molecular cloning and expression profile analysis of porcine TCAP gene.
  Mol Biol Rep, 37, 1641-1647.  
20625501 L.Tskhovrebova, and J.Trinick (2010).
Roles of titin in the structure and elasticity of the sarcomere.
  J Biomed Biotechnol, 2010, 612482.  
20133654 S.Pernigo, A.Fukuzawa, M.Bertz, M.Holt, M.Rief, R.A.Steiner, and M.Gautel (2010).
Structural insight into M-band assembly and mechanics from the titin-obscurin-like-1 complex.
  Proc Natl Acad Sci U S A, 107, 2908-2913.
PDB codes: 2wp3 2wwk 2wwm
20235223 T.Sadikot, C.R.Hammond, and M.B.Ferrari (2010).
Distinct roles for telethonin N-versus C-terminus in sarcomere assembly and maintenance.
  Dev Dyn, 239, 1124-1135.  
20414364 V.Kollár, D.Szatmári, L.Grama, and M.S.Kellermayer (2010).
Dynamic strength of titin's Z-disk end.
  J Biomed Biotechnol, 2010, 838530.  
  19789381 A.Kontrogianni-Konstantopoulos, M.A.Ackermann, A.L.Bowman, S.V.Yap, and R.J.Bloch (2009).
Muscle giants: molecular scaffolds in sarcomerogenesis.
  Physiol Rev, 89, 1217-1267.  
19622741 M.Bertz, M.Wilmanns, and M.Rief (2009).
The titin-telethonin complex is a directed, superstable molecular bond in the muscle Z-disk.
  Proc Natl Acad Sci U S A, 106, 13307.  
18996015 N.Pinotsis, P.Abrusci, K.Djinović-Carugo, and M.Wilmanns (2009).
Terminal assembly of sarcomeric filaments by intermolecular beta-sheet formation.
  Trends Biochem Sci, 34, 33-39.  
19830582 P.K.Luther (2009).
The vertebrate muscle Z-disc: sarcomere anchor for structure and signalling.
  J Muscle Res Cell Motil, 30, 171-185.  
19666561 R.S.Rock (2009).
A new direction for titin pulling.
  Proc Natl Acad Sci U S A, 106, 13149-13150.  
19679566 R.Zhang, J.Yang, J.Zhu, and X.Xu (2009).
Depletion of zebrafish Tcap leads to muscular dystrophy via disrupting sarcomere-membrane interaction, not sarcomere assembly.
  Hum Mol Genet, 18, 4130-4140.  
19771334 T.K.Kerppola (2009).
Visualization of molecular interactions using bimolecular fluorescence complementation analysis: characteristics of protein fragment complementation.
  Chem Soc Rev, 38, 2876-2886.  
18579686 A.L.Bowman, D.H.Catino, J.C.Strong, W.R.Randall, A.Kontrogianni-Konstantopoulos, and R.J.Bloch (2008).
The rho-guanine nucleotide exchange factor domain of obscurin regulates assembly of titin at the Z-disk through interactions with Ran binding protein 9.
  Mol Biol Cell, 19, 3782-3792.  
18330906 A.L.Stout, J.Wang, J.M.Sanger, and J.W.Sanger (2008).
Tracking changes in Z-band organization during myofibrillogenesis with FRET imaging.
  Cell Motil Cytoskeleton, 65, 353-367.  
18272787 C.T.Pappas, N.Bhattacharya, J.A.Cooper, and C.C.Gregorio (2008).
Nebulin interacts with CapZ and regulates thin filament architecture within the Z-disc.
  Mol Biol Cell, 19, 1837-1847.  
18212128 E.von Castelmur, M.Marino, D.I.Svergun, L.Kreplak, Z.Ucurum-Fotiadis, P.V.Konarev, A.Urzhumtsev, D.Labeit, S.Labeit, and O.Mayans (2008).
A regular pattern of Ig super-motifs defines segmental flexibility as the elastic mechanism of the titin chain.
  Proc Natl Acad Sci U S A, 105, 1186-1191.
PDB codes: 2rik 2rjm 3b43
17894348 I.Hudáky, and A.Perczel (2008).
Prolylproline unit in model peptides and in fragments from databases.
  Proteins, 70, 1389-1407.  
18948002 M.Olivé, A.Shatunov, L.Gonzalez, O.Carmona, D.Moreno, L.G.Quereda, J.A.Martinez-Matos, L.G.Goldfarb, and I.Ferrer (2008).
Transcription-terminating mutation in telethonin causing autosomal recessive muscular dystrophy type 2G in a European patient.
  Neuromuscul Disord, 18, 929-933.  
18059477 N.Pinotsis, S.Lange, J.C.Perriard, D.I.Svergun, and M.Wilmanns (2008).
Molecular basis of the C-terminal tail-to-tail assembly of the sarcomeric filament protein myomesin.
  EMBO J, 27, 253-264.
PDB code: 2r15
17496052 E.H.Lee, J.Hsin, O.Mayans, and K.Schulten (2007).
Secondary and tertiary structure elasticity of titin Z1Z2 and a titin chain model.
  Biophys J, 93, 1719-1735.  
17804417 L.Deshmukh, S.Tyukhtenko, J.Liu, J.E.Fox, J.Qin, and O.Vinogradova (2007).
Structural insight into the interaction between platelet integrin alphaIIbbeta3 and cytoskeletal protein skelemin.
  J Biol Chem, 282, 32349-32356.
PDB code: 2jtd
17074808 M.Moza, L.Mologni, R.Trokovic, G.Faulkner, J.Partanen, and O.Carpén (2007).
Targeted deletion of the muscular dystrophy gene myotilin does not perturb muscle structure or function in mice.
  Mol Cell Biol, 27, 244-252.  
17366640 P.J.Cavnar, S.G.Olenych, and T.C.Keller (2007).
Molecular identification and localization of cellular titin, a novel titin isoform in the fibroblast stress fiber.
  Cell Motil Cytoskeleton, 64, 418-433.  
16531234 E.H.Lee, M.Gao, N.Pinotsis, M.Wilmanns, and K.Schulten (2006).
Mechanical strength of the titin Z1Z2-telethonin complex.
  Structure, 14, 497-509.  
16531221 J.C.Smith (2006).
Tight in titin.
  Structure, 14, 389-390.  
16971897 K.E.Davies, and K.J.Nowak (2006).
Molecular mechanisms of muscular dystrophies: old and new players.
  Nat Rev Mol Cell Biol, 7, 762-773.  
16896432 M.Gao, M.Sotomayor, E.Villa, E.H.Lee, and K.Schulten (2006).
Molecular mechanisms of cellular mechanics.
  Phys Chem Chem Phys, 8, 3692-3706.  
17084280 M.Hoshijima, R.Knöll, M.Pashmforoush, and K.R.Chien (2006).
Reversal of calcium cycling defects in advanced heart failure toward molecular therapy.
  J Am Coll Cardiol, 48, A15-A23.  
16962974 M.Marino, P.Zou, D.Svergun, P.Garcia, C.Edlich, B.Simon, M.Wilmanns, C.Muhle-Goll, and O.Mayans (2006).
The Ig doublet Z1Z2: a model system for the hybrid analysis of conformational dynamics in Ig tandems from titin.
  Structure, 14, 1437-1447.
PDB code: 2a38
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 codes are shown on the right.