The Structure of an Interdomain Complex That Regulates Talin Activity
Talin is a large flexible rod-shaped protein that activates the integrin family of cell adhesion molecules and couples them to cytoskeletal actin. It exists in both globular and extended conformations, and an intramolecular interaction between the N-terminal F3 FERM subdomain and the C-terminal part of the talin rod contributes to an autoinhibited form of the molecule. Here, we report the solution structure of the primary F3 binding domain within the C-terminal region of the talin rod and use intermolecular nuclear Overhauser effects to determine the structure of the complex. The rod domain (residues 1655–1822) is an amphipathic five-helix bundle; Tyr-377 of F3 docks into a hydrophobic pocket at one end of the bundle, whereas a basic loop in F3 (residues 316–326) interacts with a cluster of acidic residues in the middle of helix 4. Mutation of Glu-1770 abolishes binding. The rod domain competes with β3-integrin tails for binding to F3, and the structure of the complex suggests that the rod is also likely to sterically inhibit binding of the FERM domain to the membrane. Talin is a large flexible rod-shaped protein that activates the integrin family of cell adhesion molecules and couples them to cytoskeletal actin. It exists in both globular and extended conformations, and an intramolecular interaction between the N-terminal F3 FERM subdomain and the C-terminal part of the talin rod contributes to an autoinhibited form of the molecule. Here, we report the solution structure of the primary F3 binding domain within the C-terminal region of the talin rod and use intermolecular nuclear Overhauser effects to determine the structure of the complex. The rod domain (residues 1655–1822) is an amphipathic five-helix bundle; Tyr-377 of F3 docks into a hydrophobic pocket at one end of the bundle, whereas a basic loop in F3 (residues 316–326) interacts with a cluster of acidic residues in the middle of helix 4. Mutation of Glu-1770 abolishes binding. The rod domain competes with β3-integrin tails for binding to F3, and the structure of the complex suggests that the rod is also likely to sterically inhibit binding of the FERM domain to the membrane. The cytoskeletal protein talin has emerged as a key player, both in regulating the affinity of the integrin family of cell adhesion molecules for ligand (1Calderwood D.A. J. Cell Sci. 2004; 117: 657-666Crossref PubMed Scopus (401) Google Scholar) and in coupling integrins to the actin cytoskeleton (2Critchley D.R. Gingras A.R. J. Cell Sci. 2008; 121: 1345-1347Crossref PubMed Scopus (174) Google Scholar). Thus, depletion of talin results in defects in integrin activation (3Tadokoro S. Shattil S.J. Eto K. Tai V. Liddington R.C. de Pereda J.M. Ginsberg M.H. Calderwood D.A. Science. 2003; 302: 103-106Crossref PubMed Scopus (999) Google Scholar), integrin signaling through focal adhesion kinase, the maintenance of cell spreading, and the assembly of focal adhesions in cultured cells (4Zhang X. Jiang G. Cai Y. Monkley S.J. Critchley D.R. Sheetz M.P. Nat. Cell Biol. 2008; Google Scholar). In the whole organism, studies on the single talin gene in worms (5Cram E.J. Clark S.G. Schwarzbauer J.E. J. Cell Sci. 2003; 116: 3871-3878Crossref PubMed Scopus (93) Google Scholar) and flies (6Tanentzapf G. Martin-Bermudo M.D. Hicks M.S. Brown N.H. J. Cell Sci. 2006; 119: 1632-1644Crossref PubMed Scopus (51) Google Scholar) show that talin is essential for a variety of integrin-mediated events that are crucial for normal embryonic development. In vertebrates, there are two talin genes, and mice carrying a talin1 null allele fail to complete gastrulation (7Monkley S.J. Zhou X.H. Kinston S.J. Giblett S.M. Hemmings L. Priddle H. Brown J.E. Pritchard C.A. Critchley D.R. Fassler R. Dev. Dyn. 2000; 219: 560-574Crossref PubMed Scopus (180) Google Scholar). Tissue-specific inactivation of talin1 results in an inability to activate integrins in platelets (8Nieswandt B. Moser M. Pleines I. Varga-Szabo D. Monkley S. Critchley D. Fassler R. J. Exp. Med. 2007; 204: 3113-3118Crossref PubMed Scopus (207) Google Scholar, 9Petrich B.G. Marchese P. Ruggeri Z.M. Spiess S. Weichert R.A. Ye F. Tiedt R. Skoda R.C. Monkley S.J. Critchley D.R. Ginsberg M.H. J. Exp. Med. 2007; 204: 3103-3111Crossref PubMed Scopus (233) Google Scholar), defects in the membrane-cytoskeletal interface in megakaryocytes (10Wang Y. Litvinov R.I. Chen X. Bach T.L. Lian L. Petrich B.G. Monkley S.J. Critchley D.R. Sasaki T. Birnbaum M.J. Weisel J.W. Hartwig J. Abrams C.S. J. Clin. Investig. 2008; 118: 812-819PubMed Google Scholar), and disruption of the myotendinous junction in skeletal muscle (11Conti F.J. Felder A. Monkley S. Schwander M. Wood M.R. Lieber R. Critchley D. Muller U. Development (Camb.). 2008; 135: 2043-2053Crossref PubMed Scopus (42) Google Scholar). In contrast, mice homozygous for a talin2 gene trap allele have no phenotype, although the allele may be hypomorphic (12Chen N.T. Lo S.H. Biochem. Biophys. Res. Commun. 2005; 337: 670-676Crossref PubMed Scopus (20) Google Scholar). Recent structural studies have provided substantial insights into the molecular basis of talin action. Talin is composed of an N-terminal globular head (∼50 kDa) linked to an extended flexible rod (∼220 kDa). The talin head contains a FERM 2The abbreviations used are: FERM, four-point-one, ezrin, radixin, moesin; HADDOCK, high ambiguity driven biomolecular docking; HSQC, heteronuclear single quantum coherence; NOESY, nuclear Overhauser enhancement spectroscopy; PIPKI, phosphatidylinositol-4-phosphate 5-kinase type 1. domain (made up of F1, F2, and F3 subdomains) preceded by a domain referred to here as F0 (2Critchley D.R. Gingras A.R. J. Cell Sci. 2008; 121: 1345-1347Crossref PubMed Scopus (174) Google Scholar). Studies by Wegener et al. (30Wegener K.L. Partridge A.W. Han J. Pickford A.R. Liddington R.C. Ginsberg M.H. Campbell I.D. Cell. 2007; 128: 171-182Abstract Full Text Full Text PDF PubMed Scopus (538) Google Scholar) have shown how the F3 FERM subdomain, which has a phosphotyrosine binding domain fold, interacts with both the canonical NPXY motif and the membrane-proximal helical region of the cytoplasmic tails of integrin β-subunits (13Wegener K.L. Campbell I.D. Mol. Membr. Biol. 2008; 25: 376-387Crossref PubMed Scopus (100) Google Scholar). The latter interaction apparently activates the integrin by disrupting the salt bridge between the integrin α- and β-subunit tails that normally keeps integrins locked in a low affinity state. The observation that the F0 region is also important in integrin activation (14Bouaouina M. Lad Y. Calderwood D.A. J. Biol. Chem. 2008; 283: 6118-6125Abstract Full Text Full Text PDF PubMed Scopus (116) Google Scholar) may be explained by our recent finding that F0 binds, albeit with low affinity, Rap1-GTP, 3B. T. Goult, P. R. Elliott, N. Bate, B. Patel, A. R. Gingras, J. G. Grossmann, G. C. K. Roberts, D. R. Critchley, and I. L. Barsukov, manuscript in preparation. a known activator of integrins (15Bos J.L. Curr. Opin. Cell Biol. 2005; 17: 123-128Crossref PubMed Scopus (401) Google Scholar, 16Han J. Lim C.J. Watanabe N. Soriani A. Ratnikov B. Calderwood D.A. Puzon-McLaughlin W. Lafuente E.M. Boussiotis V.A. Shattil S.J. Ginsberg M.H. Curr. Biol. 2006; 16: 1796-1806Abstract Full Text Full Text PDF PubMed Scopus (372) Google Scholar). The talin rod is made up of a series of amphipathic α-helical bundles (17Papagrigoriou E. Gingras A.R. Barsukov I.L. Bate N. Fillingham I.J. Patel B. Frank R. Ziegler W.H. Critchley D.R. J. J. 2004; PubMed Scopus Google Scholar, I. Gingras A.R. E. Patel B. J. Critchley D.R. Barsukov I.L. (Camb.). 2005; Full Text Full Text PDF PubMed Scopus Google Scholar, A.R. Ziegler W.H. Patel B. J. Critchley D.R. Barsukov I.L. 2006; PubMed Scopus Google Scholar, A.R. Bate N. L. I. H. N. D. Barsukov I.L. Critchley D.R. J. 2008; PubMed Scopus Google Scholar) and contains a integrin binding A.R. Ziegler W.H. D. M. S. A. Patel B. Bate N. J. Barsukov I.L. Liddington R.C. Ginsberg M.H. Critchley D.R. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar), binding for the cytoskeletal protein A.R. Ziegler W.H. Frank R. Barsukov I.L. Critchley D.R. J. J. Biol. Chem. 2005; Full Text Full Text PDF PubMed Scopus Google Scholar), at two actin binding L. V. S.J. Patel B. Priddle H. J.E. Critchley D.R. J. Cell Sci. PubMed Google Scholar), and a C-terminal helix that is for assembly of talin A.R. Bate N. L. I. H. N. D. Barsukov I.L. Critchley D.R. J. 2008; PubMed Scopus Google Scholar, S.J. 2007; PubMed Scopus Google Scholar). V. C. S. C. F. A. M.R. C. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar) and studies J. Lim C.J. Watanabe N. Soriani A. Ratnikov B. Calderwood D.A. Puzon-McLaughlin W. Lafuente E.M. Boussiotis V.A. Shattil S.J. Ginsberg M.H. Curr. Biol. 2006; 16: 1796-1806Abstract Full Text Full Text PDF PubMed Scopus (372) Google Scholar) that the integrin binding in talin are and both and have in It is that of the FERM domain family of are by a interaction A. D. R. D. Cell Dev. Biol. 2000; 16: PubMed Scopus Google and studies show that talin is globular in low salt although is in in high salt L. D. J. B. K. J. Biol. Chem. Full Text PDF PubMed Google Scholar). contrast, the talin rod talin by is in both that the head is for talin to a state. for an interaction between the talin head and rod has emerged studies by et al. E. X. X. D. J. Cell. 2008; Full Text Full Text PDF PubMed Scopus Google Scholar), binding of talin F3 to a talin rod residues an interaction that by E. X. X. D. J. Cell. 2008; Full Text Full Text PDF PubMed Scopus Google Scholar). also that of the talin rod the binding in F3 for the helix of the β3-integrin E. X. X. D. J. Cell. 2008; Full Text Full Text PDF PubMed Scopus Google Scholar), the talin interaction in regulating the integrin binding of et al. E. X. X. D. J. Cell. 2008; Full Text Full Text PDF PubMed Scopus Google Scholar) the F3 binding in rod into two with affinity residues and affinity residues Here, we the rod domain and determine the structure of residues a five-helix show that domain F3 residues on helix with an affinity to the high affinity by et al. E. X. X. D. J. Cell. 2008; Full Text Full Text PDF PubMed Scopus Google Scholar). also report the structure of the complex between F3 and the rod domain and show that the latter the known binding in F3 for the β3-integrin and is to inhibit the of the talin FERM domain with the membrane. of β3-integrin as I. Campbell I.D. Wegener K.L. J. Biol. Chem. 2008; 283: Full Text Full Text PDF PubMed Scopus Google Scholar). of Talin talin1 residues and by a talin1 as and into the Talin in cultured in for protein in for of for talin by The by with and the by F3 and F3 made as (30Wegener K.L. Partridge A.W. Han J. Pickford A.R. Liddington R.C. Ginsberg M.H. Campbell I.D. Cell. 2007; 128: 171-182Abstract Full Text Full Text PDF PubMed Scopus (538) Google Scholar). at on the to as talin talin F3, integrin for the and structure of talin with protein in of the at both with to and and J. F. E. J.L. J. PubMed Scopus Google Scholar). with and W. A. M. J.L. J. 2005; PubMed Scopus Google Scholar). and used for the of the and and The of have in the with the to the between talin and the β3-integrin on a with a and in and F. S. G. J. A. J. PubMed Scopus Google Scholar), and as J. F. E. J.L. J. PubMed Scopus Google Scholar). The and of β3-integrin I. Campbell I.D. Wegener K.L. J. Biol. Chem. 2008; 283: Full Text Full Text PDF PubMed Scopus Google Scholar). the and on in with and used to the G. F. A. J. PubMed Scopus Google Scholar). within structure of structure on the of M.P. J. Mol. Biol. PubMed Scopus Google Scholar) a series of to with the T. P. K. J. PubMed Scopus Google Scholar) for and used as in structure by M. PubMed Scopus Google Scholar). The in the of to to and for with the by and to be to the at the and used for The in the of The Scholar). The structural for domain are in 1. The of has to the with the structure of talin in for the in in for the in for in in for the in for in in a in and the and are for the and and A. Y. Nat. Biol. PubMed Scopus Google Scholar), and by the in with to the is the is the at and and are the protein and ligand with the to by of in the of talin F3 talin and as of talin to F3 with the C. R. J. Chem. 2003; PubMed Scopus Google Scholar, S.J. M. M. A. V. T. 2007; PubMed Scopus Google Scholar). The of the F3 complex with the (30Wegener K.L. Partridge A.W. Han J. Pickford A.R. Liddington R.C. Ginsberg M.H. Campbell I.D. Cell. 2007; 128: 171-182Abstract Full Text Full Text PDF PubMed Scopus (538) Google Scholar) and the structure of talin and used to the residues to The between Tyr-377 in F3 and and of talin also used in the In complex by and the by for and in an for is as C. R. J. Chem. 2003; PubMed Scopus Google Scholar). the of the F3 in the Talin of the talin residues has shown to two binding for the talin F3 FERM subdomain E. X. X. D. J. Cell. 2008; Full Text Full Text PDF PubMed Scopus Google Scholar). the molecular basis of the we the domain of the of the talin which is made up of a of into bundles have that the C-terminal (residues which contains an actin binding A.R. Bate N. L. I. H. N. D. Barsukov I.L. Critchley D.R. J. 2008; PubMed Scopus Google Scholar), is preceded by two five-helix (residues and that up the integrin binding referred to as A.R. Ziegler W.H. D. M. S. A. Patel B. Bate N. J. Barsukov I.L. Liddington R.C. Ginsberg M.H. Critchley D.R. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar). the the which contains a binding to be a (residues A.R. Ziegler W.H. Patel B. J. Critchley D.R. Barsukov I.L. 2006; PubMed Scopus Google Scholar), we have that is as a five-helix (residues T. Goult, A. R. Gingras, N. Bate, G. C. K. Roberts, I. L. Barsukov, and D. R. Critchley, domain by one the F3 binding by et al. E. X. X. D. J. Cell. 2008; Full Text Full Text PDF PubMed Scopus Google Scholar) (residues the domain is also a five-helix bundle, we residues a region that is in both talin1 and talin2 and The protein and as by for a the of a domain and with with a state. of Talin solution structure of talin and The structure of amphipathic a by hydrophobic and The between and and and are whereas between and and and are of the residues in helix and in helix that in the are talin The of the is to that in talin (17Papagrigoriou E. Gingras A.R. Barsukov I.L. Bate N. Fillingham I.J. Patel B. Frank R. Ziegler W.H. Critchley D.R. J. J. 2004; PubMed Scopus Google Scholar) and the two bundles in talin which up A.R. Ziegler W.H. D. M. S. A. Patel B. Bate N. J. Barsukov I.L. Liddington R.C. Ginsberg M.H. Critchley D.R. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar). The is hydrophobic with a by the hydrophobic of and The in the is a talin bundles (17Papagrigoriou E. Gingras A.R. Barsukov I.L. Bate N. Fillingham I.J. Patel B. Frank R. Ziegler W.H. Critchley D.R. J. J. 2004; PubMed Scopus Google Scholar, I. Gingras A.R. E. Patel B. J. Critchley D.R. Barsukov I.L. (Camb.). 2005; Full Text Full Text PDF PubMed Scopus Google Scholar, A.R. Ziegler W.H. Patel B. J. Critchley D.R. Barsukov I.L. 2006; PubMed Scopus Google Scholar, A.R. Bate N. L. I. H. N. D. Barsukov I.L. Critchley D.R. J. 2008; PubMed Scopus Google Scholar), there is no the end of the of the domain is that there is a hydrophobic on and and that is by the loop between and which contains hydrophobic residues and that into It to be hydrophobic is a for interaction in the rod (17Papagrigoriou E. Gingras A.R. Barsukov I.L. Bate N. Fillingham I.J. Patel B. Frank R. Ziegler W.H. Critchley D.R. J. J. 2004; PubMed Scopus Google Scholar). Talin with the Talin F3 interaction between the talin rod five-helix and the F3 FERM subdomain of the talin head by of talin in the of of F3 of in an is shown in of the for residues and a for the complex of in with that for the E. X. X. D. J. Cell. 2008; Full Text Full Text PDF PubMed Scopus Google Scholar). The in talin by F3 are shown as a of in and are on the structure in and E. The binding for F3 on talin is is on helix and the C-terminal end of helix of the five-helix The residues in the rod binding are The results of the of talin to F3, are shown in The are a of F3 in and are to by et al. E. X. X. D. J. Cell. 2008; Full Text Full Text PDF PubMed Scopus Google Scholar) a talin of the between Talin and Talin of the complex C. R. J. Chem. 2003; PubMed Scopus Google Scholar, S.J. M. M. A. V. T. 2007; PubMed Scopus Google Scholar) on the basis of and intermolecular The latter by two one of talin in complex with the talin F3 subdomain, and one of F3 in complex with talin intermolecular of which be the two in with talin to F3 and The intermolecular to the of and of talin with the the of the of Tyr-377 of F3 large on the of talin and intermolecular are between and the of and of talin The on of the two of the intramolecular that the of the two on complex The of the complex is shown in The F3 binding on talin is a large and with two interaction Thus, Tyr-377 of F3 docks into a hydrophobic pocket on talin whereas the F3 activation loop (residues 316–326) the helical helix 4. The activation loop of F3 has a high of and and is in on binding talin as by the large of residues in region and with a residues to between and the The structure of the complex that the on with which the activation loop interacts has with an and with residues and to form with the basic residues in F3 The of and the of F3, in the of in Talin the F3 F3 the interface between the two we made a series of of talin and to the interaction with on the structure of the complex the and the between as an and to be that that of the protein The with the which F3 no with a of F3 and The of Glu-1770 are by F3, and is in an for an to a in the activation loop of the structure of the the likely is of and on helix which are in the binding no on F3 binding The N. S. S. J. Mol. Biol. PubMed Scopus Google Scholar) that residues in the may be and on helix is to Glu-1770 and may to the of the Mutation of to in a large in affinity for F3 on although the the interaction of F3 with helix residues in helix and effects with the the a for in regulating the interaction between F3 and the rod has to be in talin B. C. Han J. J. Ginsberg M.H. J. Cell Sci. 2005; 118: PubMed Scopus Google Scholar) and is in to the binding pocket for Tyr-377 of F3 a effects on the interaction with F3 that of is also in of the of in Talin F3 the Talin Talin of of the talin F3 domain also in form and for binding to the talin rod by Tyr-377 in F3 a hydrophobic binding pocket on the of talin as shown by intermolecular to residues and Mutation of Tyr-377 to in an in binding affinity, with in the complex The structure of the talin complex also suggests a interaction between in F3 and in the talin rod In of a substantial binding talin and the in a large in affinity et al. E. X. X. D. J. Cell. 2008; Full Text Full Text PDF PubMed Scopus Google Scholar) that of in F3 affinity for the talin and talin as in in cells as The that the the talin interaction and results in a of talin the E. X. X. D. J. Cell. 2008; Full Text Full Text PDF PubMed Scopus Google Scholar). our that is in the talin the complex and no are to talin of the F3 with talin that has a on binding It is that talin is in talin head on E. X. X. D. J. Cell. 2008; Full Text Full Text PDF PubMed Scopus Google Scholar), that the have the we that results in a in the affinity of the talin head for the β3-integrin cytoplasmic domain with for the Talin with the for to between F3 and the membrane-proximal region of the β3-integrin have shown to be to talin and for integrin activation (30Wegener K.L. Partridge A.W. Han J. Pickford A.R. Liddington R.C. Ginsberg M.H. Campbell I.D. Cell. 2007; 128: 171-182Abstract Full Text Full Text PDF PubMed Scopus (538) Google Scholar). The structure of the complex that talin to the binding in F3 for the membrane-proximal part of the β3-integrin whereas that for the NPXY part is with the results of and with a talin and a E. X. X. D. J. Cell. 2008; Full Text Full Text PDF PubMed Scopus Google Scholar). to the single talin domain with the β3-integrin for binding to the F3 The and of the β3-integrin have I. Campbell I.D. Wegener K.L. J. Biol. Chem. 2008; 283: Full Text Full Text PDF PubMed Scopus Google Scholar), and the of in a be on the of talin The of F3 large both in the NPXY region (residues and in the membrane-proximal of the In contrast, the of talin to the of interaction between the talin rod and the β3-integrin the F3 domain in the of a of talin the of the residues of the β3-integrin with the F3 domain between the β3-integrin and talin for binding to the F3 in and to one region of the integrin the talin rod which F3 at to with F3 for binding to the β3-integrin studies by et al. L. D. J. B. K. J. Biol. Chem. Full Text PDF PubMed Google Scholar) that talin in both extended and globular and that the globular is on an interaction between the talin head and rod It is the recent studies of et al. E. X. X. D. J. Cell. 2008; Full Text Full Text PDF PubMed Scopus Google Scholar) that globular is at in part to an interaction between the talin F3 FERM subdomain and residues of the talin rod the provided for two F3 binding one of which (residues a affinity for F3 the (residues have the domain of the region that the high affinity and the solution structure of domain (residues as as a of complex with the F3 The affinity by et al. E. X. X. D. J. Cell. 2008; Full Text Full Text PDF PubMed Scopus Google Scholar) we have we have to binding of F3 to The that F3 to the suggests that although the primary F3 binding in the talin rod residues affinity with in the the affinity of the It is also that of the talin head to binding. have shown that the F3 binding on talin is two one Tyr-377 of F3 into a hydrophobic pocket at the of the helical and a that basic residues in the activation loop of F3, which to a cluster of residues on helix of talin suggests that helix region is the important in of binding the to a in Tyr-377 may a in regulating binding is to be a N. S. S. J. Mol. Biol. PubMed Scopus Google Scholar). of Tyr-377 to a in affinity, of a in have a the hydrophobic of the binding pocket on talin the of the talin complex with that of F3 to a (30Wegener K.L. Partridge A.W. Han J. Pickford A.R. Liddington R.C. Ginsberg M.H. Campbell I.D. Cell. 2007; 128: 171-182Abstract Full Text Full Text PDF PubMed Scopus (538) Google Scholar), is that the talin rod domain a on F3 to the β3-integrin and the β3-integrin membrane-proximal region a to and of talin F3 the is in the the interaction region for both on F3 is the the of binding is the talin interaction is by whereas the talin interaction is hydrophobic in our show that the binding for the NPXY region of the integrin in F3 is by the talin rod in with the by et al. E. X. X. D. J. Cell. 2008; Full Text Full Text PDF PubMed Scopus Google Scholar), although between integrin for talin and talin that binding be the at the of to in F3 I.L. A. Bate N. Patel B. N. K. G. P. Critchley D.R. J. Biol. Chem. 2003; Full Text Full Text PDF PubMed Scopus Google Scholar, Pereda J.M. Wegener K.L. E. Bate N. Ginsberg M.H. Critchley D.R. Campbell I.D. Liddington R.C. J. Biol. Chem. 2005; Full Text Full Text PDF PubMed Scopus Google Scholar), and has shown to a key in the of cytoplasmic which is to be in the autoinhibited to the K. R.A. PubMed Scopus Google Scholar, K. M.D. R.A. J. Cell Biol. 2003; PubMed Scopus Google Scholar). The binding of talin to F3 may also the interaction of F3 and of the talin FERM domain with the membrane. which in a loop between and of F3, is important in integrin and has that interacts with acidic the complex (30Wegener K.L. Partridge A.W. Han J. Pickford A.R. Liddington R.C. Ginsberg M.H. Campbell I.D. Cell. 2007; 128: 171-182Abstract Full Text Full Text PDF PubMed Scopus (538) Google Scholar). The structure of the domain complex that interaction be the basic on the FERM subdomain may also with acidic the FERM domain at the interface and integrin binding. the basis of the structure of the domain B. de Pereda J.M. Calderwood D.A. Critchley D. Campbell I.D. Ginsberg M.H. Liddington R.C. Cell. 2003; Full Text Full Text PDF PubMed Scopus Google Scholar), the binding of the rod domain to F3 be to an In the talin complex here a structural basis for talin The the that to talin and K. R.A. PubMed Scopus Google Scholar, K. M.D. R.A. J. Cell Biol. 2003; PubMed Scopus Google Scholar), the and binding J. Lim C.J. Watanabe N. Soriani A. Ratnikov B. Calderwood D.A. Puzon-McLaughlin W. Lafuente E.M. Boussiotis V.A. Shattil S.J. Ginsberg M.H. Curr. Biol. 2006; 16: 1796-1806Abstract Full Text Full Text PDF PubMed Scopus (372) Google Scholar, Lim C.J. Puzon-McLaughlin W. Shattil S.J. Ginsberg M.H. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar) have in with