Distinct Binding Modes of Vinculin Isoforms Underlie Their Functional Differences

Andrey Krokhotin, Muzaddid Sarker, Ernesto Alva Sevilla, Lindsey M. Costantini, Jack D. Griffith, Sharon L. Campbell, Nikolay V. Dokholyan

Research output: Contribution to journalArticle

Abstract

Vinculin and its splice isoform metavinculin play key roles in regulating cellular morphology, motility, and force transduction. Vinculin is distinct from metavinculin in its ability to bundle filamentous actin (F-actin). To elucidate the molecular basis for these differences, we employed computational and experimental approaches. Results from these analyses suggest that the C terminus of both vinculin and metavinculin form stable interactions with the F-actin surface. However, the metavinculin tail (MVt) domain contains a 68 amino acid insert, with helix 1 (H1) sequestered into a globular subdomain, which protrudes from the F-actin surface and prevents actin bundling by sterically occluding actin filaments. Consistent with our model, deletion and selective point mutations within the MVt H1 disrupt this protruding structure, and facilitate actin bundling similar to vinculin tail (Vt) domain.

Original languageEnglish (US)
Pages (from-to)1527-1536.e3
JournalStructure
Volume27
Issue number10
DOIs
StatePublished - Oct 1 2019

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Vinculin
Actins
Protein Isoforms
Actin Cytoskeleton
Point Mutation
metavinculin
Amino Acids

All Science Journal Classification (ASJC) codes

  • Structural Biology
  • Molecular Biology

Cite this

Krokhotin, A., Sarker, M., Sevilla, E. A., Costantini, L. M., Griffith, J. D., Campbell, S. L., & Dokholyan, N. V. (2019). Distinct Binding Modes of Vinculin Isoforms Underlie Their Functional Differences. Structure, 27(10), 1527-1536.e3. https://doi.org/10.1016/j.str.2019.07.013
Krokhotin, Andrey ; Sarker, Muzaddid ; Sevilla, Ernesto Alva ; Costantini, Lindsey M. ; Griffith, Jack D. ; Campbell, Sharon L. ; Dokholyan, Nikolay V. / Distinct Binding Modes of Vinculin Isoforms Underlie Their Functional Differences. In: Structure. 2019 ; Vol. 27, No. 10. pp. 1527-1536.e3.
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Krokhotin, A, Sarker, M, Sevilla, EA, Costantini, LM, Griffith, JD, Campbell, SL & Dokholyan, NV 2019, 'Distinct Binding Modes of Vinculin Isoforms Underlie Their Functional Differences', Structure, vol. 27, no. 10, pp. 1527-1536.e3. https://doi.org/10.1016/j.str.2019.07.013

Distinct Binding Modes of Vinculin Isoforms Underlie Their Functional Differences. / Krokhotin, Andrey; Sarker, Muzaddid; Sevilla, Ernesto Alva; Costantini, Lindsey M.; Griffith, Jack D.; Campbell, Sharon L.; Dokholyan, Nikolay V.

In: Structure, Vol. 27, No. 10, 01.10.2019, p. 1527-1536.e3.

Research output: Contribution to journalArticle

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Krokhotin A, Sarker M, Sevilla EA, Costantini LM, Griffith JD, Campbell SL et al. Distinct Binding Modes of Vinculin Isoforms Underlie Their Functional Differences. Structure. 2019 Oct 1;27(10):1527-1536.e3. https://doi.org/10.1016/j.str.2019.07.013