title: A zyxin head-tail interaction regulates zyxin-VASP complex formation.
abstract: Zyxin is an adhesion protein that regulates actin assembly by binding to VASP family members through N-terminal proline-rich motifs. Evidence suggests that zyxin's C-terminal LIM domains function as a negative regulator of zyxin-VASP complexes. Zyxin LIM domains access to binding partners is negatively regulated by an unknown mechanism. One possibility is that zyxin LIM domains mediate a head-tail interaction, blocking interactions with other proteins. Such a mechanism might prevent both zyxin-VASP complexes activity and LIM domain access. In this report, the effect of LIM domains on zyxin-VASP complex assembly is defined. We find that zyxin LIM domains associate with zyxin's VASP binding sites, preventing zyxin from binding to PKA-phosphorylated VASP. Unphosphorylated VASP overcomes the head-tail interaction, a result of a direct interaction with the LIM domain region. Zyxin, like a growing number of actin regulators, is controlled by intramolecular interactions.
authors.affiliation: Physiology and Developmental Biology, Brigham Young University, 574 WIDB, Provo, UT 84602, USA.
authors.forename: James D
authors.initials: JD
authors.lastname: Moody
authors.forename: Jacob
authors.initials: J
authors.lastname: Grange
authors.forename: Marc P A
authors.initials: MP
authors.lastname: Ascione
authors.forename: Dustin
authors.initials: D
authors.lastname: Boothe
authors.forename: Erica
authors.initials: E
authors.lastname: Bushnell
authors.forename: Marc D H
authors.initials: MD
authors.lastname: Hansen
mesh_terms: D015815:Cell Adhesion Molecules / Q000737:chemistry / Q000378:metabolism*; D003598:Cytoskeletal Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006023:Glycoproteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008840:Microfilament Proteins / Q000737:chemistry / Q000378:metabolism*; D010750:Phosphoproteins / Q000737:chemistry / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D060589:Zyxin; D000098662:Vasodilator-Stimulated Phosphoprotein
chemical_list: D015815:Cell Adhesion Molecules; D003598:Cytoskeletal Proteins; D006023:Glycoproteins; D008840:Microfilament Proteins; D010750:Phosphoproteins; C092842:ZYX protein, human; D060589:Zyxin; D000098662:Vasodilator-Stimulated Phosphoprotein