PDBsum entry 1rkc

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protein Protein-protein interface(s) links
Cell adhesion, structural protein PDB id
Protein chains
258 a.a. *
26 a.a. *
* Residue conservation analysis
PDB id:
Name: Cell adhesion, structural protein
Title: Human vinculin head (1-258) in complex with talin's vinculin binding site 3 (residues 1944-1969)
Structure: Vinculin. Chain: a. Fragment: vinculin head (residues 1-258). Engineered: yes. Talin. Chain: b. Fragment: binding site 3 (residues 1944-1969). Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: vcl. Expressed in: escherichia coli. Expression_system_taxid: 562. Gallus gallus. Chicken. Organism_taxid: 9031.
Biol. unit: Dimer (from PQS)
2.70Å     R-factor:   0.244     R-free:   0.335
Authors: T.Izard,G.Evans,R.A.Borgon,C.L.Rush,G.Bricogne,P.R.Bois
Key ref:
T.Izard et al. (2004). Vinculin activation by talin through helical bundle conversion. Nature, 427, 171-175. PubMed id: 14702644 DOI: 10.1038/nature02281
21-Nov-03     Release date:   13-Jan-04    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
P18206  (VINC_HUMAN) -  Vinculin
1134 a.a.
258 a.a.
Protein chain
Pfam   ArchSchema ?
P54939  (TLN1_CHICK) -  Talin-1
2541 a.a.
26 a.a.
Key:    PfamA 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: 10.1038/nature02281 Nature 427:171-175 (2004)
PubMed id: 14702644  
Vinculin activation by talin through helical bundle conversion.
T.Izard, G.Evans, R.A.Borgon, C.L.Rush, G.Bricogne, P.R.Bois.
Vinculin is a conserved component and an essential regulator of both cell-cell (cadherin-mediated) and cell-matrix (integrin-talin-mediated focal adhesions) junctions, and it anchors these adhesion complexes to the actin cytoskeleton by binding to talin in integrin complexes or to alpha-actinin in cadherin junctions. In its resting state, vinculin is held in a closed conformation through interactions between its head (Vh) and tail (Vt) domains. The binding of vinculin to focal adhesions requires its association with talin. Here we report the crystal structures of human vinculin in its inactive and talin-activated states. Talin binding induces marked conformational changes in Vh, creating a novel helical bundle structure, and this alteration actively displaces Vt from Vh. These results, as well as the ability of alpha-actinin to also bind to Vh and displace Vt from pre-existing Vh-Vt complexes, support a model whereby Vh functions as a domain that undergoes marked structural changes that allow vinculin to direct cytoskeletal assembly in focal adhesions and adherens junctions. Notably, talin's effects on Vh structure establish helical bundle conversion as a signalling mechanism by which proteins direct cellular responses.
  Selected figure(s)  
Figure 3.
Figure 3: Structure of inactive human vinculin. a, Cartoon representation of the closed conformation of vinculin (Vh, residues 1 -258, pink; Vt, 879 -1066, light blue). b, c, Electrostatic surface potential (red, negative; blue, positive) of the Vh -Vt complex. b, Head-on view of each interface (left, Vh; right, Vt) when Vh and Vt are taken apart (that is, Vh is rotated 90 to the left and Vt is rotated 90 to the right with respect to the orientation shown in a). Residues involved in interdomain contacts are labelled. c, Same orientation as in a, revealing the acidic pocket created when Vh binds to Vt. Acidic residues lining the pocket are indicated in yellow.
Figure 4.
Figure 4: Structure of Vh when activated by talin. a, Electrostatic surface potential (red, negative; blue, positive) of Vh when bound to talin. Talin VBS3 is shown in ball-and-stick representation (oxygen atoms, red; carbon, yellow; nitrogen, blue; bonds, black). b, The C-terminal bundle (helices 4 -7) of active (red) and inactive (pink) Vh are superimposed (back view of Fig. 3a). Talin VBS3, dark blue; Vt, light blue. c, Movements and helical distortions (green arrows) of the helices ( 1 -4) of the N-terminal bundle of inactive Vh (pink) occurring on activation of Vh (red) by talin VBS3 (dark blue). Helices H1 -5 of inactive Vt (grey) are shown when bound to Vh (pink).
  The above figures are reprinted by permission from Macmillan Publishers Ltd: Nature (2004, 427, 171-175) copyright 2004.  
  Figures were selected by the author.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21487611 G.J.Pound, A.A.Pletnev, X.Fang, and E.V.Pletneva (2011).
A small fluorophore reporter of protein conformation and redox state.
  Chem Commun (Camb), 47, 5714-5716.  
20949625 L.D.Nagaprashantha, R.Vatsyayan, P.C.Lelsani, S.Awasthi, and S.S.Singhal (2011).
The sensors and regulators of cell-matrix surveillance in anoikis resistance of tumors.
  Int J Cancer, 128, 743-752.  
20668527 C.F.Dibble, J.A.Horst, M.H.Malone, K.Park, B.Temple, H.Cheeseman, J.R.Barbaro, G.L.Johnson, and S.Bencharit (2010).
Defining the functional domain of programmed cell death 10 through its interactions with phosphatidylinositol-3,4,5-trisphosphate.
  PLoS One, 5, e11740.  
20502710 E.S.Rangarajan, J.H.Lee, S.D.Yogesha, and T.Izard (2010).
A helix replacement mechanism directs metavinculin functions.
  PLoS One, 5, e10679.
PDB code: 3myi
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.  
20086044 X.Peng, L.E.Cuff, C.D.Lawton, and K.A.DeMali (2010).
Vinculin regulates cell-surface E-cadherin expression by binding to beta-catenin.
  J Cell Sci, 123, 567-577.  
  19952892 A.Zemljic-Harpf, A.M.Manso, and R.S.Ross (2009).
Vinculin and talin: focus on the myocardium.
  J Investig Med, 57, 849-855.  
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.  
19350419 C.T.Mierke (2009).
The role of vinculin in the regulation of the mechanical properties of cells.
  Cell Biochem Biophys, 53, 115-126.  
19416068 D.R.Critchley (2009).
Biochemical and structural properties of the integrin-associated cytoskeletal protein talin.
  Annu Rev Biophys, 38, 235-254.  
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.  
19098287 H.S.Lee, C.J.Lim, W.Puzon-McLaughlin, S.J.Shattil, and M.H.Ginsberg (2009).
RIAM Activates Integrins by Linking Talin to Ras GTPase Membrane-targeting Sequences.
  J Biol Chem, 284, 5119-5127.  
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
19110481 S.M.Palmer, M.P.Playford, S.W.Craig, M.D.Schaller, and S.L.Campbell (2009).
Lipid Binding to the Tail Domain of Vinculin: SPECIFICITY AND THE ROLE OF THE N AND C TERMINI.
  J Biol Chem, 284, 7223-7231.  
19217273 V.Vogel, and M.P.Sheetz (2009).
Cell fate regulation by coupling mechanical cycles to biochemical signaling pathways.
  Curr Opin Cell Biol, 21, 38-46.  
18650496 N.O.Deakin, and C.E.Turner (2008).
Paxillin comes of age.
  J Cell Sci, 121, 2435-2444.  
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.  
17785437 A.E.Zemljic-Harpf, J.C.Miller, S.A.Henderson, A.T.Wright, A.M.Manso, L.Elsherif, N.D.Dalton, A.K.Thor, G.A.Perkins, A.D.McCulloch, and R.S.Ross (2007).
Cardiac-myocyte-specific excision of the vinculin gene disrupts cellular junctions, causing sudden death or dilated cardiomyopathy.
  Mol Cell Biol, 27, 7522-7537.  
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
17928215 M.A.Arnaout, S.L.Goodman, and J.P.Xiong (2007).
Structure and mechanics of integrin-based cell adhesion.
  Curr Opin Cell Biol, 19, 495-507.  
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.  
17077085 S.Johnson, P.Roversi, M.Espina, A.Olive, J.E.Deane, S.Birket, T.Field, W.D.Picking, A.J.Blocker, E.E.Galyov, W.L.Picking, and S.M.Lea (2007).
Self-chaperoning of the type III secretion system needle tip proteins IpaD and BipD.
  J Biol Chem, 282, 4035-4044.
PDB codes: 2cmq 2ixr 2j0n 2j0o 2j9t 2jaa
16930976 A.Bershadsky, M.Kozlov, and B.Geiger (2006).
Adhesion-mediated mechanosensitivity: a time to experiment, and a time to theorize.
  Curr Opin Cell Biol, 18, 472-481.  
16407302 B.Patel, A.R.Gingras, A.A.Bobkov, L.M.Fujimoto, M.Zhang, R.C.Liddington, D.Mazzeo, J.Emsley, G.C.Roberts, I.L.Barsukov, and D.R.Critchley (2006).
The activity of the vinculin binding sites in talin is influenced by the stability of the helical bundles that make up the talin rod.
  J Biol Chem, 281, 7458-7467.  
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
  16569237 D.L.Scott, G.Diez, and W.H.Goldmann (2006).
Protein-lipid interactions: correlation of a predictive algorithm for lipid-binding sites with three-dimensional structural data.
  Theor Biol Med Model, 3, 17.  
16608855 D.M.Cohen, B.Kutscher, H.Chen, D.B.Murphy, and S.W.Craig (2006).
A conformational switch in vinculin drives formation and dynamics of a talin-vinculin complex at focal adhesions.
  J Biol Chem, 281, 16006-16015.  
17074767 H.Chen, D.M.Choudhury, and S.W.Craig (2006).
Coincidence of actin filaments and talin is required to activate vinculin.
  J Biol Chem, 281, 40389-40398.  
16437158 N.Pashkova, Y.Jin, S.Ramaswamy, and L.S.Weisman (2006).
Structural basis for myosin V discrimination between distinct cargoes.
  EMBO J, 25, 693-700.
PDB code: 2f6h
16407299 P.R.Bois, B.P.O'Hara, D.Nietlispach, J.Kirkpatrick, and T.Izard (2006).
The vinculin binding sites of talin and alpha-actinin are sufficient to activate vinculin.
  J Biol Chem, 281, 7228-7236.  
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.  
16891659 Y.Chen, and N.V.Dokholyan (2006).
Insights into allosteric control of vinculin function from its large scale conformational dynamics.
  J Biol Chem, 281, 29148-29154.  
16135522 A.R.Gingras, W.H.Ziegler, R.Frank, I.L.Barsukov, G.C.Roberts, D.R.Critchley, and J.Emsley (2005).
Mapping and consensus sequence identification for multiple vinculin binding sites within the talin rod.
  J Biol Chem, 280, 37217-37224.
PDB codes: 1zvz 1zw2 1zw3
15728584 D.M.Cohen, H.Chen, R.P.Johnson, B.Choudhury, and S.W.Craig (2005).
Two distinct head-tail interfaces cooperate to suppress activation of vinculin by talin.
  J Biol Chem, 280, 17109-17117.  
15883197 H.Chen, D.M.Cohen, D.M.Choudhury, N.Kioka, and S.W.Craig (2005).
Spatial distribution and functional significance of activated vinculin in living cells.
  J Cell Biol, 169, 459-470.  
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
15795225 K.Briknarová, F.Nasertorabi, M.L.Havert, E.Eggleston, D.W.Hoyt, C.Li, A.J.Olson, K.Vuori, and K.R.Ely (2005).
The serine-rich domain from Crk-associated substrate (p130cas) is a four-helix bundle.
  J Biol Chem, 280, 21908-21914.
PDB code: 1z23
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
15635447 T.H.Millard, G.Bompard, M.Y.Heung, T.R.Dafforn, D.J.Scott, L.M.Machesky, and K.Fütterer (2005).
Structural basis of filopodia formation induced by the IRSp53/MIM homology domain of human IRSp53.
  EMBO J, 24, 240-250.
PDB code: 1y2o
16113084 T.Shemesh, B.Geiger, A.D.Bershadsky, and M.M.Kozlov (2005).
Focal adhesions as mechanosensors: a physical mechanism.
  Proc Natl Acad Sci U S A, 102, 12383-12388.  
15366705 A.Kobielak, and E.Fuchs (2004).
Alpha-catenin: at the junction of intercellular adhesion and actin dynamics.
  Nat Rev Mol Cell Biol, 5, 614-625.  
15468300 A.Y.Lee, B.C.Park, M.Jang, S.Cho, D.H.Lee, S.C.Lee, P.K.Myung, and S.G.Park (2004).
Identification of caspase-3 degradome by two-dimensional gel electrophoresis and matrix-assisted laser desorption/ionization-time of flight analysis.
  Proteomics, 4, 3429-3436.  
15195105 C.Bakolitsa, D.M.Cohen, L.A.Bankston, A.A.Bobkov, G.W.Cadwell, L.Jennings, D.R.Critchley, S.W.Craig, and R.C.Liddington (2004).
Structural basis for vinculin activation at sites of cell adhesion.
  Nature, 430, 583-586.
PDB code: 1st6
15103147 C.L.Rush, and T.Izard (2004).
Rhombohedral crystals of the human vinculin head domain in complex with a vinculin-binding site of talin.
  Acta Crystallogr D Biol Crystallogr, 60, 945-947.  
15572774 E.Blanc, P.Roversi, C.Vonrhein, C.Flensburg, S.M.Lea, and G.Bricogne (2004).
Refinement of severely incomplete structures with maximum likelihood in BUSTER-TNT.
  Acta Crystallogr D Biol Crystallogr, 60, 2210-2221.  
15272303 E.Papagrigoriou, A.R.Gingras, I.L.Barsukov, N.Bate, I.J.Fillingham, B.Patel, R.Frank, W.H.Ziegler, G.C.Roberts, D.R.Critchley, and J.Emsley (2004).
Activation of a vinculin-binding site in the talin rod involves rearrangement of a five-helix bundle.
  EMBO J, 23, 2942-2951.
PDB codes: 1sj7 1sj8 1t01
15501673 K.A.Demali (2004).
Vinculin--a dynamic regulator of cell adhesion.
  Trends Biochem Sci, 29, 565-567.  
15031296 L.Tremuth, S.Kreis, C.Melchior, J.Hoebeke, P.Rondé, S.Plançon, K.Takeda, and N.Kieffer (2004).
A fluorescence cell biology approach to map the second integrin-binding site of talin to a 130-amino acid sequence within the rod domain.
  J Biol Chem, 279, 22258-22266.  
15138291 M.C.Subauste, O.Pertz, E.D.Adamson, C.E.Turner, S.Junger, and K.M.Hahn (2004).
Vinculin modulation of paxillin-FAK interactions regulates ERK to control survival and motility.
  J Cell Biol, 165, 371-381.  
15159399 S.Witt, A.Zieseniss, U.Fock, B.M.Jockusch, and S.Illenberger (2004).
Comparative biochemical analysis suggests that vinculin and metavinculin cooperate in muscular adhesion sites.
  J Biol Chem, 279, 31533-31543.  
15070891 T.Izard, and C.Vonrhein (2004).
Structural basis for amplifying vinculin activation by talin.
  J Biol Chem, 279, 27667-27678.
PDB code: 1syq
15229287 Z.Zhang, G.Izaguirre, S.Y.Lin, H.Y.Lee, E.Schaefer, and B.Haimovich (2004).
The phosphorylation of vinculin on tyrosine residues 100 and 1065, mediated by SRC kinases, affects cell spreading.
  Mol Biol Cell, 15, 4234-4247.  
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.