spacer
spacer

PDBsum entry 1zw2
Go to PDB code: 
protein Protein-protein interface(s) links
Protein binding PDB id
1zw2

 

 

 

 

Loading ...

 
JSmol PyMol  
Contents
Protein chains
251 a.a. *
21 a.a. *
Waters ×77
* Residue conservation analysis
PDB id:
1zw2
Name: Protein binding
Title: Vinculin head (0-258) in complex with the talin rod residues 2345-2369
Structure: Vinculin. Chain: a. Synonym: metavinculin. Engineered: yes. Talin. Chain: b. Engineered: yes
Source: Gallus gallus. Chicken. Organism_taxid: 9031. Gene: vcl, vinc1. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008. Synthetic: yes. Other_details: the peptide was chemically synthesized. The sequence of the peptide is naturally found in gallus gallus (chicken).
Biol. unit: Dimer (from PQS)
Resolution:
2.10Å     R-factor:   0.257     R-free:   0.295
Authors: A.R.Gingras,W.H.Ziegler,I.L.Barsukov,G.C.Roberts,D.R.Critchley, J.Emsley
Key ref:
A.R.Gingras et al. (2005). Mapping and consensus sequence identification for multiple vinculin binding sites within the talin rod. J Biol Chem, 280, 37217-37224. PubMed id: 16135522 DOI: 10.1074/jbc.M508060200
Date:
03-Jun-05     Release date:   20-Sep-05    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P12003  (VINC_CHICK) -  Vinculin from Gallus gallus
Seq:
Struc: 		 
Seq:
Struc: 		 
Seq:
Struc: 		1135 a.a.
251 a.a.
Protein chain
Pfam   ArchSchema ?
P54939  (TLN1_CHICK) -  Talin-1 from Gallus gallus
Seq:
Struc: 		 
Seq:
Struc: 		 
Seq:
Struc: 		 
Seq:
Struc: 		 
Seq:
Struc: 		 
Seq:
Struc: 		2541 a.a.
21 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 

 
DOI no: 10.1074/jbc.M508060200 J Biol Chem 280:37217-37224 (2005)
PubMed id: 16135522  
 
 
Mapping and consensus sequence identification for multiple vinculin binding sites within the talin rod.
A.R.Gingras, W.H.Ziegler, R.Frank, I.L.Barsukov, G.C.Roberts, D.R.Critchley, J.Emsley.
 
  ABSTRACT  
 
The interaction between the cytoskeletal proteins talin and vinculin plays a key role in integrin-mediated cell adhesion and migration. Three vinculin binding sites (VBS1-3) have previously been identified in the talin rod using a yeast two-hybrid assay. To extend these studies, we spot-synthesized a series of peptides spanning all the alpha-helical regions predicted for the talin rod and identified eight additional VBSs, two of which overlap key functional regions of the rod, including the integrin binding site and C-terminal actin binding site. The talin VBS alpha-helices bind to a hydrophobic cleft in the N-terminal vinculin Vd1 domain. We have defined the specificity of this interaction by spot-synthesizing a series of 25-mer talin VBS1 peptides containing substitutions with all the commonly occurring amino acids. The consensus for recognition is LXXAAXXVAXX- VXXLIXXA with distinct classes of hydrophobic side chains at positions 1, 4, 5, 8, 9, 12, 15, and 16 required for vinculin binding. Positions 1, 8, 12, 15, and 16 require an aliphatic residue and will not tolerate alanine, whereas positions 4, 5, and 9 are less restrictive. These preferences are common to all 11 VBS sequences with a minor variation occurring in one case. A crystal structure of this variant VBS peptide in complex with the vinculin Vd1 domain reveals a subtly different mode of vinculin binding.
 
  Selected figure(s)  
 
Figure 2.
FIGURE 2. Relative distribution of the VBS peptides among the 63 predicted -helices which make up the talin rod. Vinculin binding helices are shown in blue and non-binders in gray. VBS1-3 (peptides 4, 12, and 46) were previously mapped using a yeast two-hybrid assay (21). The black line indicates the position of an integrin binding site (residues 1984-2113) (18), and the red line the C-terminal actin binding site (residues 2295-2541) (19, 20). 		Figure 5.
FIGURE 5. Analysis of talin VBS rule violations. A, alignment of talin peptides with sequences that do not conform with the position-specific preferences for vinculin binding defined in Fig. 4. Residues on a gray background align with the highly buried (>75%) hydrophobic side chains from the talin VBS1·vinculin Vd1 complex crystal structure. Residues that would be predicted to knock out binding of VBS1 to vinculin (Fig. 4) are indicated in white. Included are weak/borderline vinculin binding VBS peptides and also two non-binding peptides 5 and 21, which appear to conform to the VBS consensus. All of the strong binders conform to the rules except peptides 11 and 12 (VBS2). From the weak binders, only peptides 36 and 60 have no rule violations. B, conversion of VBS2 (peptide 12) into a strong vinculin binder by substituting residues from VBS1 (peptide 4). Note the negative influence of Thr and Met in positions 12 and 15.
 
  The above figures are reprinted by permission from the ASBMB: J Biol Chem (2005, 280, 37217-37224) copyright 2005.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20610383 A.R.Gingras, N.Bate, B.T.Goult, B.Patel, P.M.Kopp, J.Emsley, I.L.Barsukov, G.C.Roberts, and D.R.Critchley (2010).
Central region of talin has a unique fold that binds vinculin and actin.
  J Biol Chem, 285, 29577-29587.
PDB code: 2x0c
20399778 B.T.Goult, A.R.Gingras, N.Bate, I.L.Barsukov, D.R.Critchley, and G.C.Roberts (2010).
The domain structure of talin: residues 1815-1973 form a five-helix bundle containing a cryptic vinculin-binding site.
  FEBS Lett, 584, 2237-2241.
PDB code: 2kvp
20605055 P.M.Kopp, N.Bate, T.M.Hansen, N.P.Brindle, U.Praekelt, E.Debrand, S.Coleman, D.Mazzeo, B.T.Goult, A.R.Gingras, C.A.Pritchard, D.R.Critchley, and S.J.Monkley (2010).
Studies on the morphology and spreading of human endothelial cells define key inter- and intramolecular interactions for talin1.
  Eur J Cell Biol, 89, 661-673.  
20644727 S.Marg, U.Winkler, M.Sestu, M.Himmel, M.Schönherr, J.Bär, A.Mann, M.Moser, C.T.Mierke, K.Rottner, M.Blessing, J.Hirrlinger, and W.H.Ziegler (2010).
The vinculin-DeltaIn20/21 mouse: characteristics of a constitutive, actin-binding deficient splice variant of vinculin.
  PLoS One, 5, e11530.  
19176533 A.R.Gingras, W.H.Ziegler, A.A.Bobkov, M.G.Joyce, D.Fasci, M.Himmel, S.Rothemund, A.Ritter, J.G.Grossmann, B.Patel, N.Bate, B.T.Goult, J.Emsley, I.L.Barsukov, G.C.Roberts, R.C.Liddington, M.H.Ginsberg, and D.R.Critchley (2009).
Structural determinants of integrin binding to the talin rod.
  J Biol Chem, 284, 8866-8876.
PDB code: 3dyj
19179532 A.del Rio, R.Perez-Jimenez, R.Liu, P.Roca-Cusachs, J.M.Fernandez, and M.P.Sheetz (2009).
Stretching single talin rod molecules activates vinculin binding.
  Science, 323, 638-641.  
19297334 B.T.Goult, N.Bate, N.J.Anthis, K.L.Wegener, A.R.Gingras, B.Patel, I.L.Barsukov, I.D.Campbell, G.C.Roberts, and D.R.Critchley (2009).
The structure of an interdomain complex that regulates talin activity.
  J Biol Chem, 284, 15097-15106.
PDB codes: 2kbb 2kgx
19416068 D.R.Critchley (2009).
Biochemical and structural properties of the integrin-associated cytoskeletal protein talin.
  Annu Rev Biophys, 38, 235-254.  
19220457 E.Debrand, Y.El Jai, L.Spence, N.Bate, U.Praekelt, C.A.Pritchard, S.J.Monkley, and D.R.Critchley (2009).
Talin 2 is a large and complex gene encoding multiple transcripts and protein isoforms.
  FEBS J, 276, 1610-1628.  
19655048 G.C.Roberts, and D.R.Critchley (2009).
Structural and biophysical properties of the integrin-associated cytoskeletal protein talin.
  Biophys Rev, 1, 61-69.  
19278997 M.Himmel, A.Ritter, S.Rothemund, B.V.Pauling, K.Rottner, A.R.Gingras, and W.H.Ziegler (2009).
Control of high affinity interactions in the talin C terminus: how talin domains coordinate protein dynamics in cell adhesions.
  J Biol Chem, 284, 13832-13842.  
18157087 A.R.Gingras, N.Bate, B.T.Goult, L.Hazelwood, I.Canestrelli, J.G.Grossmann, H.Liu, N.S.Putz, G.C.Roberts, N.Volkmann, D.Hanein, I.L.Barsukov, and D.R.Critchley (2008).
The structure of the C-terminal actin-binding domain of talin.
  EMBO J, 27, 458-469.
PDB codes: 2jsw 2qdq
18408041 S.E.Lee, S.Chunsrivirot, R.D.Kamm, and M.R.Mofrad (2008).
Molecular dynamics study of talin-vinculin binding.
  Biophys J, 95, 2027-2036.  
18282082 V.P.Hytönen, and V.Vogel (2008).
How force might activate talin's vinculin binding sites: SMD reveals a structural mechanism.
  PLoS Comput Biol, 4, e24.  
17932491 G.T.Nhieu, and T.Izard (2007).
Vinculin binding in its closed conformation by a helix addition mechanism.
  EMBO J, 26, 4588-4596.
PDB code: 2ibf
16826238 C.Hamiaux, A.van Eerde, C.Parsot, J.Broos, and B.W.Dijkstra (2006).
Structural mimicry for vinculin activation by IpaA, a virulence factor of Shigella flexneri.
  EMBO Rep, 7, 794-799.
PDB code: 2gdc
16830345 S.J.Franco, M.A.Senetar, W.T.Simonson, A.Huttenlocher, and R.O.McCann (2006).
The conserved C-terminal I/LWEQ module targets Talin1 to focal adhesions.
  Cell Motil Cytoskeleton, 63, 563-581.  
16893648 W.H.Ziegler, R.C.Liddington, and D.R.Critchley (2006).
The structure and regulation of vinculin.
  Trends Cell Biol, 16, 453-460.  
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.

 

spacer
spacer