title: Central region of talin has a unique fold that binds vinculin and actin.
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.
authors.affiliation: Department of Biochemistry, University of Leicester, Lancaster Road, Leicester LE1 9HN, UK.
authors.forename: Alexandre R
authors.initials: AR
authors.lastname: Gingras
authors.forename: Neil
authors.initials: N
authors.lastname: Bate
authors.forename: Benjamin T
authors.initials: BT
authors.lastname: Goult
authors.forename: Bipin
authors.initials: B
authors.lastname: Patel
authors.forename: Petra M
authors.initials: PM
authors.lastname: Kopp
authors.forename: Jonas
authors.initials: J
authors.lastname: Emsley
authors.forename: Igor L
authors.initials: IL
authors.lastname: Barsukov
authors.forename: Gordon C K
authors.initials: GC
authors.lastname: Roberts
authors.forename: David R
authors.initials: DR
authors.lastname: Critchley
mesh_terms: D000199:Actins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001665:Binding Sites; D002645:Chickens; D002942:Circular Dichroism; D018360:Crystallography, X-Ray; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D051379:Mice; D041681:NIH 3T3 Cells; D011485:Protein Binding / Q000235:genetics / Q000502:physiology; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D016608:Talin / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D016596:Vinculin / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*
chemical_list: D000199:Actins; D016608:Talin; D016596:Vinculin