A vinculin binding domain from the talin rod unfolds to form a complex with the vinculin head.
The cytoskeletal protein talin plays a key role in activating integrins and in coupling them to the actin cytoskeleton. Its N-terminal globular head, which binds beta integrins, is linked to an extended rod having a C-terminal actin binding site and several vinculin binding sites (VBSs). The NMR structure of residues 755-889 of the rod (containing a VBS) is shown to be an amphipathic four-helix bundle with a left-handed topology. A talin peptide corresponding to the VBS binds the vinculin head; the X-ray crystallographic structure of this complex shows that the residues which interact with vinculin are buried in the hydrophobic core of the talin fragment. NMR shows that the interaction involves a major structural change in the talin fragment, including unfolding of one of its helices, making the VBS accessible to vinculin. Interestingly, the talin 755-889 fragment binds more than one vinculin head molecule, suggesting that the talin rod may contain additional as yet unrecognized VBSs.
Fillingham
Ian
I
Department of Biochemistry, University of Leicester, Leicester LE1 7RH, UK.
Gingras
Alexandre R
AR
Papagrigoriou
Evangelos
E
Patel
Bipin
B
Emsley
Jonas
J
Critchley
David R
DR
Roberts
Gordon C K
GC
Barsukov
Igor L
IL
D000199:Actins / Q000737:chemistry; D000595:Amino Acid Sequence; D001665:Binding Sites; D018360:Crystallography, X-Ray; D003598:Cytoskeletal Proteins / Q000737:chemistry; D004591:Electrophoresis, Polyacrylamide Gel; D057927:Hydrophobic and Hydrophilic Interactions; D008958:Models, Molecular; D008969:Molecular Sequence Data; D019906:Nuclear Magnetic Resonance, Biomolecular; D011485:Protein Binding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D012996:Solutions; D013059:Spectrum Analysis, Raman; D016608:Talin / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D016596:Vinculin / Q000737:chemistry* / Q000378:metabolism*
D000199:Actins; D003598:Cytoskeletal Proteins; D011994:Recombinant Proteins; D012996:Solutions; D016608:Talin; D016596:Vinculin