Central region of talin has a unique fold that binds vinculin and actin

Gingras, AR, Bate, N, Goult, BT ORCID: 0000-0002-3438-2807, Patel, B, Kopp, PM, Emsley, J, Barsukov, IL ORCID: 0000-0003-4406-9803, Roberts, GCK and Critchley, DR (2010) Central region of talin has a unique fold that binds vinculin and actin Journal of Biological Chemistry, 285 (38). pp. 29577-29587. ISSN 0021-9258, 1083-351X

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Abstract

Talin is an adaptor protein that couples integrins to F-actin. Structural studies show that the N-terminal talin head contains an atypical FERM domain, whereas the N- and C-terminal parts of the talin rod include a series of α-helical bundles. However, determining the structure of the central part of the rod has proved problematic. Residues 1359-1659 are homologous to the MESDc1 gene product, and we therefore expressed this region of talin in Escherichia coli. The crystal structure shows a unique fold comprised of a 5- and 4-helix bundle. The 5-helix bundle is composed of nonsequential helices due to insertion of the 4-helix bundle into the loop at the C terminus of helix α3. The linker connecting the bundles forms a two-stranded antiparallel β-sheet likely limiting the relative movement of the two bundles. Because the 5-helix bundle contains the N and C termini of this module, we propose that it is linked by short loops to adjacent bundles, whereas the 4-helix bundle protrudes from the rod. This suggests the 4-helix bundle has a unique role, and its pI (7.8) is higher than other rod domains. Both helical bundles contain vinculin-binding sites but that in the isolated 5-helix bundle is cryptic, whereas that in the isolated 4-helix bundle is constitutively active. In contrast, both bundles are required for actin binding. Finally,we show that the MESDc1 protein, which is predicted to have a similar fold, is a novel actin-binding protein. © 2010 by The American Society for Biochemistry and Molecular Biology, Inc.

Item Type:	Article
Additional Information:	## TULIP Type: Articles/Papers (Journal) ##
Uncontrolled Keywords:	NIH 3T3 Cells, Animals, Chickens, Mice, Escherichia coli, Actins, Talin, Vinculin, Crystallography, X-Ray, Circular Dichroism, Binding Sites, Protein Structure, Secondary, Protein Structure, Tertiary, Protein Binding
Divisions:	Faculty of Health & Life Sciences Faculty of Health & Life Sciences > Inst. Systems, Molec & Integrative Biology > Inst. Systems, Molec & Integrative Biology
Depositing User:	Symplectic Admin
Date Deposited:	13 Mar 2024 09:35
Last Modified:	24 Jan 2026 00:17
DOI:	10.1074/jbc.M109.095455
Related Websites:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3179347
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