Central region of talin has a unique fold that binds vinculin and actin
| Autor: | Igor L. Barsukov, Benjamin T. Goult, Neil Bate, Alexandre R. Gingras, Gordon C. K. Roberts, David R. Critchley, Bipin Patel, Petra M. Kopp, Jonas Emsley |
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| Rok vydání: | 2010 |
| Předmět: |
Talin
Integrins Integrin Crystallography X-Ray Biochemistry Protein Structure Secondary MESDc1 03 medical and health sciences Mice Protein structure Escherichia coli Cell Adhesion Animals Molecular Biology Actin 030304 developmental biology Helix bundle 0303 health sciences Binding Sites Crystallography FERM domain biology Synemin C-terminus Circular Dichroism 030302 biochemistry & molecular biology Cell Biology Vinculin Actins NMR Protein Structure Tertiary Bundle Helix Protein Structure and Folding biology.protein Biophysics NIH 3T3 Cells Crystal Structure Chickens Protein Binding |
| Zdroj: | The Journal of Biological Chemistry |
| ISSN: | 1083-351X |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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