Three-dimensional structure of vinculin bound to actin filaments.
Vinculin plays a pivotal role in cell adhesion and migration by providing the link between the actin cytoskeleton and the transmembrane receptors, integrin and cadherin. We used a combination of electron microscopy, computational docking, and biochemistry to provide an atomic model of how the vinculin tail binds actin filaments. The vinculin tail actin binding site comprises two distinct regions. One of these regions is exposed in the full-length autoinhibited conformation of vinculin, whereas the second site is sterically occluded by vinculin's N-terminal domain. The partial accessibility of the F-actin binding site in the autoinhibited full-length vinculin structure suggests that F-actin can act as part of a combinatorial input framework with other binding partners such as alpha-catenin or talin to induce vinculin head-tail dissociation, thus promoting vinculin activation. Furthermore, binding to F-actin potentiates a local rearrangement in the vinculin tail that in turn promotes vinculin dimerization and, hence, formation of actin bundles.
Janssen
Mandy E W
ME
Program on Cell Adhesion, The Burnham Institute for Medical Research, 10901 North Torrey Pines Road, La Jolla, California 92037, USA.
Kim
Eldar
E
Liu
Hongjun
H
Fujimoto
L Miya
LM
Bobkov
Andrey
A
Volkmann
Niels
N
Hanein
Dorit
D
D000199:Actins / Q000737:chemistry* / Q000378:metabolism* / Q000648:ultrastructure; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002645:Chickens; D019281:Dimerization; D007091:Image Processing, Computer-Assisted; D066298:In Vitro Techniques; D008854:Microscopy, Electron; D008958:Models, Molecular; D008969:Molecular Sequence Data; D046912:Multiprotein Complexes; D016296:Mutagenesis; D011485:Protein Binding; D011817:Rabbits; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D017384:Sequence Deletion; D055672:Static Electricity; D016596:Vinculin / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure; D051178:alpha Catenin / Q000378:metabolism
D000199:Actins; D046912:Multiprotein Complexes; D011993:Recombinant Fusion Proteins; D051178:alpha Catenin; D016596:Vinculin