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

Gingras, Alexandre R ORCID: 0000-0002-5373-0176, Bate, Neil, Goult, Benjamin T ORCID: 0000-0002-3438-2807, Patel, Bipin, Kopp, Petra M, Emsley, Jonas ORCID: 0000-0002-8949-8030, Barsukov, Igor L ORCID: 0000-0003-4406-9803, Roberts, Gordon CK ORCID: 0000-0001-6200-1373 and Critchley, David R (2010) Central region of talin has a unique fold that binds vinculin and actin. The Journal of biological chemistry, 285 (38). pp. 29577-29587.

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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 anti-parallel 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.

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 and Life Sciences Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology
Depositing User:	Symplectic Admin
Date Deposited:	13 Mar 2024 09:35
Last Modified:	13 Mar 2024 09:35
DOI:	10.1074/jbc.m109.095455
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3179347