Intermolecular versus intramolecular interactions of the vinculin binding site 33 of talin

Yogesha, Sollepura D; Sharff, A.; Bricogne, G.; Izard, Tina

doi:10.1002/pro.671

Cited by 9 publications

(11 citation statements)

References 38 publications

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“…1A). As first reported for Vh1 bound to talin-VBS3 (22), the minimal ␣-catenin VBS (residues 328 -352) forms an ␣-helix that binds the N-terminal 4HB of Vh1 by helix bundle conversion, as subsequently also seen for the VBSs of talin (22,28,(45)(46)(47)(48), ␣-actinin (49), and the bacterial IpaA (32,50,51) and sca4 (52) …”

Section: Structure Of Unfurled Vbd Of ␣-Catenin In Complex With Vh1-supporting

confidence: 64%

“…4B), as seen for the VBSs of talin (22,28,(45)(46)(47)(48), ␣-actinin (49), or the bacterial IpaA (32,50,51) and sca4 (52).…”

Section: Vinculin-␣-catenin Binding Is Facilitated By Severing Vinculmentioning

confidence: 77%

“…All constructs were verified by sequencing. Full-length vinculin (residues 1-1066), vinculin head (VH) (1-843), Vt (879 -1066), and Vh1 (1-252) were generated as described (23,27,28).…”

Section: Methodsmentioning

confidence: 99%

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The Cytoskeletal Protein α-Catenin Unfurls upon Binding to Vinculin

Rangarajan

Izard

2012

Journal of Biological Chemistry

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Background: ␣-Catenin provides links for cadherin receptors to the actin cytoskeleton at cell-cell adherens junctions. Results: Extensive ␣-catenin interactions with vinculin are displaced by the vinculin tail domain. Conclusion: ␣-Catenin-vinculin interactions are stabilized by F-actin. Significance: The data support a new model whereby vinculin activation at adherens junctions is sufficient to stabilize connections of ␣-catenin with the actin network.

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Section: Structure Of Unfurled Vbd Of ␣-Catenin In Complex With Vh1-supporting

confidence: 64%

“…4B), as seen for the VBSs of talin (22,28,(45)(46)(47)(48), ␣-actinin (49), or the bacterial IpaA (32,50,51) and sca4 (52).…”

Section: Vinculin-␣-catenin Binding Is Facilitated By Severing Vinculmentioning

confidence: 77%

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The Cytoskeletal Protein α-Catenin Unfurls upon Binding to Vinculin

Rangarajan

Izard

2012

Journal of Biological Chemistry

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“…Nevertheless, the B-factors for the R7R8-bound TBS1 and Vd1-bound TBS1 are strikingly different, suggesting that the TBS1 fragment prefers the more stable kinked helical conformation. Talin also possesses 11 vinculin binding sites (VBS) that bind to the Vd1 domain with much higher affinity than that of the Vd1 and TBS1 (Gingras et al, 2005; Goult et al, 2013b; Rees et al, 1990; Yogesha et al, 2011). Thus, it appears that the interaction of RIAM and vinculin is rather transient and the main function of RIAM TBS1 is to recruit cytoplasmic talin to the PM.…”

Section: Discussionmentioning

confidence: 99%

Structural and Mechanistic Insights into the Recruitment of Talin by RIAM in Integrin Signaling

et al. 2014

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Plasma membrane (PM)-bound GTPase Rap1 recruits the Rap1-interacting-adaptor-molecule (RIAM), which in turn recruits talin to bind and activate integrins. However, it is unclear how RIAM recruits talin and why its close homolog lamellipodin does not. Here we report that, although RIAM possesses two talin-binding sites (TBS1 and TBS2), only TBS1 is capable of recruiting cytoplasmic talin to the PM, and the R8 domain is the strongest binding site in talin. Crystal structure of an R7R8:TBS1 complex reveals an unexpected kink in the TBS1 helix that is not shared in the homologous region of lamellipodin. This kinked helix conformation is required for the co-localization of RIAM and talin at the PM and proper activation of integrin. Our findings provide the structural and mechanistic insight into talin recruitment by RIAM that underlies integrin activation and explain the differential functions of the otherwise highly homologous RIAM and lamellipodin in integrin signaling.

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“…Further, the proline-rich hinge binds to the vasodilator-stimulated phosphoprotein VASP, vinexin-β, and the Arp2/3 complex to control actin dynamics at adhesion sites and thus cell migration (26)(27)(28). Our structures of activated vinculin in complex with the vinculin binding sites (VBSs) of talin (14,15,29,30), α-actinin (16), or IpaA (31)(32)(33) showed that binding of these VBSs severs the vinculin head-tail interaction and displaces Vt allosterically. Originally, PIP 2 was thought to sever the VH-Vt interaction (34)(35)(36), but the VBSs of talin and α-actinin, or those of the IpaA invasin of Shigella, are sufficient to activate vinculin, whereas mechanical stretching of a single talin molecule activates vinculin (37).…”

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confidence: 99%

Differential lipid binding of vinculin isoforms promotes quasi-equivalent dimerization

Chinthalapudi

Rangarajan

Brown

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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The main cause of death globally remains debilitating heart conditions, such as dilated cardiomyopathy (DCM) and hypertrophic cardiomyopathy (HCM), which are often due to mutations of specific components of adhesion complexes. Vinculin regulates these complexes and plays essential roles in intercalated discs that are necessary for muscle cell function and coordinated movement and in the development and function of the heart. Humans bearing familial or sporadic mutations in vinculin suffer from chronic, progressively debilitating DCM that ultimately leads to cardiac failure and death, whereas autosomal dominant mutations in vinculin can also provoke HCM, causing acute cardiac failure. The DCM/HCM-associated mutants of vinculin occur in the 68-residue insert unique to the muscle-specific, alternatively spliced isoform of vinculin, termed metavinculin (MV). Contrary to studies that suggested that phosphoinositol-4,5-bisphosphate (PIP 2 ) only induces vinculin homodimers, which are asymmetric, we show that phospholipid binding results in a domain-swapped symmetric MV dimer via a quasi-equivalent interface compared with vinculin involving R975. Although one of the two PIP 2 binding sites is preserved, the symmetric MV dimer that bridges two PIP 2 molecules differs from the asymmetric vinculin dimer that bridges only one PIP 2 . Unlike vinculin, wild-type MV and the DCM/ HCM-associated R975W mutant bind PIP 2 in their inactive conformations, and R975W MV fails to dimerize. Mutating selective vinculin residues to their corresponding MV residues, or vice versa, switches the isoform's dimeric constellation and lipid binding site. Collectively, our data suggest that MV homodimerization modulates microfilament attachment at muscular adhesion sites and furthers our understanding of MV-mediated cardiac remodeling.ardiomyopathies are a major worldwide health problem, with patients often suffering cardiac arrest and premature death. Over the past decade, several inherited and sporadic mutations in genes encoding components of adhesion complexes and of intercalated discs, which are required for the coordinated movement of heart tissue, have been pinpointed as the cause of many cardiomyopathies. Vinculin and its muscle-specific splice variant, metavinculin (MV), are essential and highly conserved cytoskeletal proteins that play critical regulatory roles in cell-cell adherens-type junctions and cell-matrix focal adhesions (1-3). Both isoforms localize to the cell membrane, the I band in the sarcomere, and to intercalated discs (4). MV is coexpressed with vinculin (5) and colocalizes with vinculin in cardiac myocytes (6). MV only differs from vinculin by an insertion of 68 residues between α-helices H1 and H2 of the 5-helix bundle vinculin tail domain Vt (5, 7), whereby H1′ of the insert of MV structurally replaces H1 of vinculin. Several MV mutations have been shown to be associated with dilated cardiomyopathies (DCMs) and hypertrophic cardiomyopathies (HCMs) in human (8-10), where they disrupt intercalated discs in the hearts of...

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Intermolecular versus intramolecular interactions of the vinculin binding site 33 of talin

Cited by 9 publications

References 38 publications

The Cytoskeletal Protein α-Catenin Unfurls upon Binding to Vinculin

The Cytoskeletal Protein α-Catenin Unfurls upon Binding to Vinculin

Structural and Mechanistic Insights into the Recruitment of Talin by RIAM in Integrin Signaling

Differential lipid binding of vinculin isoforms promotes quasi-equivalent dimerization

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