A zyxin head-tail interaction regulates zyxin-VASP complex formation.
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.
Moody
James D
JD
Physiology and Developmental Biology, Brigham Young University, 574 WIDB, Provo, UT 84602, USA.
Grange
Jacob
J
Ascione
Marc P A
MP
Boothe
Dustin
D
Bushnell
Erica
E
Hansen
Marc D H
MD
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
D015815:Cell Adhesion Molecules; D003598:Cytoskeletal Proteins; D006023:Glycoproteins; D008840:Microfilament Proteins; D010750:Phosphoproteins; C092842:ZYX protein, human; D060589:Zyxin; D000098662:Vasodilator-Stimulated Phosphoprotein