Crystal structure of the vinculin tail suggests a pathway for activation

Vinculin plays a dynamic role in the assembly of the actin cytoskeleton. A strong interaction between its head and tail domains that regulates binding to other cytoskeletal components is disrupted by acidic phospholipids. Here, we present the crystal structure of the vinculin tail, residues 879-1066...

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Bibliographic Details
Published in:Cell 1999-12, Vol.99 (6), p.603-613
Main Authors: Bakolitsa, C, de Pereda, J M, Bagshaw, C R, Critchley, D R, Liddington, R C
Format: Article
Language:English
Subjects:
Actins - chemistry
Amino Acid Sequence
Animals
Apolipoproteins - metabolism
Chickens
Crystallography
Cytoskeleton - chemistry
Models, Biological
Models, Molecular
Molecular Sequence Data
Phospholipids - metabolism
Protein Binding
Protein Structure, Quaternary
Protein Structure, Secondary
Sequence Homology, Amino Acid
Vinculin - chemistry
Vinculin - metabolism
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Summary:Vinculin plays a dynamic role in the assembly of the actin cytoskeleton. A strong interaction between its head and tail domains that regulates binding to other cytoskeletal components is disrupted by acidic phospholipids. Here, we present the crystal structure of the vinculin tail, residues 879-1066. Five amphipathic helices form an antiparallel bundle that resembles exchangeable apolipoproteins. A C-terminal arm wraps across the base of the bundle and emerges as a hydrophobic hairpin surrounded by a collar of basic residues, adjacent to the N terminus. We show that the C-terminal arm is required for binding to acidic phospholipids but not to actin, and that binding either ligand induces conformational changes that may represent the first step in activation.
ISSN:0092-8674
DOI:10.1016/s0092-8674(00)81549-4