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PDBsum entry 1syq

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protein Protein-protein interface(s) links
Cell adhesion PDB id
1syq
Jmol
Contents
Protein chains
259 a.a. *
25 a.a. *
Waters ×190
* Residue conservation analysis
PDB id:
1syq
Name: Cell adhesion
Title: Human vinculin head domain vh1, residues 1-258, in complex w talin's vinculin binding site 1, residues 607-636
Structure: Vinculin isoform vcl. Chain: a. Engineered: yes. Talin 1. Chain: b. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli bl21. Expression_system_taxid: 511693. Synthetic: yes
Biol. unit: Dodecamer (from PQS)
Resolution:
2.42Å     R-factor:   0.188     R-free:   0.236
Authors: T.Izard,C.Vonrhein
Key ref:
T.Izard and C.Vonrhein (2004). Structural basis for amplifying vinculin activation by talin. J Biol Chem, 279, 27667-27678. PubMed id: 15070891 DOI: 10.1074/jbc.M403076200
Date:
01-Apr-04     Release date:   20-Jul-04    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P18206  (VINC_HUMAN) -  Vinculin
Seq:
Struc:
 
Seq:
Struc:
 
Seq:
Struc:
1134 a.a.
259 a.a.
Protein chain
Pfam   ArchSchema ?
Q9Y490  (TLN1_HUMAN) -  Talin-1
Seq:
Struc:
 
Seq:
Struc:
 
Seq:
Struc:
 
Seq:
Struc:
 
Seq:
Struc:
 
Seq:
Struc:
2541 a.a.
25 a.a.
Key:    PfamA domain  PfamB domain  Secondary structure  CATH domain

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     actin cytoskeleton   1 term 
  Biological process     cell adhesion   1 term 
  Biochemical function     structural molecule activity     1 term  

 

 
DOI no: 10.1074/jbc.M403076200 J Biol Chem 279:27667-27678 (2004)
PubMed id: 15070891  
 
 
Structural basis for amplifying vinculin activation by talin.
T.Izard, C.Vonrhein.
 
  ABSTRACT  
 
Talin interactions with vinculin are essential for focal adhesions. Curiously, talin contains three noncontiguous vinculin binding sites (VBS) that can bind individually to the vinculin head (Vh) domain. Here we report the crystal structure of the human Vh.VBS1 complex, a validated model of the Vh.VBS2 structure, and biochemical studies that demonstrate that all of talin VBSs activate vinculin by provoking helical bundle conversion of the Vh domain, which displaces the vinculin tail (Vt) domain. Thus, helical bundle conversion is a structurally conserved response in talin-vinculin interactions. Furthermore, talin VBSs bind to Vh in a mutually exclusive manner but do differ in their affinity for Vh and in their ability to displace Vt, suggesting that the strengths of these interactions could lead to differences in signaling outcome. These findings support a model in which talin binds to and activates multiple vinculin molecules to provoke rapid reorganization of the actin cytoskeleton.
 
  Selected figure(s)  
 
Figure 2.
FIG. 2. Helical bundle conversion provoked by binding of talin VBSs is a conserved response. Stereo C superimposition of Vh when bound by talin VBS1 (in pink, VBS1 is shown in teal) versus when bound by talin VBS3 (in red; VBS3 is shown in dark blue). For clarity, only a few C positions are labeled.
Figure 3.
FIG. 3. Model of the Vh·VBS2 complex. A, sequence alignment of the three human vinculin binding sites (VBS1, VBS2, and VBS3) of talin. Residues identical in all three VBSs are boxed in red, and conserved residues are boxed in yellow. Asterisks indicate variant residues in VBS2 which reduce its ability to displace Vt from Vh·Vt complexes. B, stereo superimposition of the modeled VBS2 (yellow) when bound to Vh (not shown) versus VBS1 (in teal) as seen in the Vh·VBS1 crystal structure. Residues contributing to the interactions of talin VBS1 and Vh are underlined. Italicized residues are those proposed to reduce the ability of VBS2 to displace Vt compared with VBS1. C, electrostatic surface potential (51) of VBS2 (residues 855-874) as modeled when bound to Vh (red, negative; blue, positive; white, uncharged). Left and right images are presented in the same orientation as shown in D for VBS1. D, electrostatic surface potential of VBS1 (only equivalent residues 607-626 are shown) as seen in the Vh·VBS1 crystal structure. The right image shows the solvent-exposed VBS1 surface, and the left image shows the surface buried upon binding to Vh.
 
  The above figures are reprinted by permission from the ASBMB: J Biol Chem (2004, 279, 27667-27678) copyright 2004.  
  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
20222986 L.Zhang, X.Jia, X.Zhang, J.Sun, X.Peng, T.Qi, F.Ma, L.Yin, Y.Yao, C.Qiu, and H.Lu (2010).
Proteomic analysis of PBMCs: characterization of potential HIV-associated proteins.
  Proteome Sci, 8, 12.  
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.  
19416068 D.R.Critchley (2009).
Biochemical and structural properties of the integrin-associated cytoskeletal protein talin.
  Annu Rev Biophys, 38, 235-254.  
19523901 J.H.Lee, E.S.Rangarajan, S.D.Yogesha, and T.Izard (2009).
Raver1 interactions with vinculin and RNA suggest a feed-forward pathway in directing mRNA to focal adhesions.
  Structure, 17, 833-842.
PDB codes: 3h2u 3h2v
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
17183545 M.A.Senetar, C.L.Moncman, and R.O.McCann (2007).
Talin2 is induced during striated muscle differentiation and is targeted to stable adhesion complexes in mature muscle.
  Cell Motil Cytoskeleton, 64, 157-173.  
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.  
17088427 T.Izard, G.Tran Van Nhieu, and P.R.Bois (2006).
Shigella applies molecular mimicry to subvert vinculin and invade host cells.
  J Cell Biol, 175, 465-475.
PDB codes: 2gww 2hsq
16893648 W.H.Ziegler, R.C.Liddington, and D.R.Critchley (2006).
The structure and regulation of vinculin.
  Trends Cell Biol, 16, 453-460.  
15642262 I.Fillingham, A.R.Gingras, E.Papagrigoriou, B.Patel, J.Emsley, D.R.Critchley, G.C.Roberts, and I.L.Barsukov (2005).
A vinculin binding domain from the talin rod unfolds to form a complex with the vinculin head.
  Structure, 13, 65-74.
PDB codes: 1u6h 1u89 1xwx
15988023 P.R.Bois, R.A.Borgon, C.Vonrhein, and T.Izard (2005).
Structural dynamics of alpha-actinin-vinculin interactions.
  Mol Cell Biol, 25, 6112-6122.
PDB code: 1ydi
16252250 R.L.Rich, and D.G.Myszka (2005).
Survey of the year 2004 commercial optical biosensor literature.
  J Mol Recognit, 18, 431-478.  
15501673 K.A.Demali (2004).
Vinculin--a dynamic regulator of cell adhesion.
  Trends Biochem Sci, 29, 565-567.  
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.