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Title: Plakophilin-3 Binds the Membrane and Filamentous Actin without Bundling F-Actin
Plakophilin-3 is a ubiquitously expressed protein found widely in epithelial cells and is a critical component of desmosomes. The plakophilin-3 carboxy-terminal domain harbors nine armadillo repeat motifs with largely unknown functions. Here, we report the 5 Å cryogenic electron microscopy (cryoEM) structure of the armadillo repeat motif domain of plakophilin-3, one of the smaller cryoEM structures reported to date. We find that this domain is a monomer or homodimer in solution. In addition, using an in vitro actin co-sedimentation assay, we show that the armadillo repeat domain of plakophilin-3 directly interacts with F-actin. This feature, through direct interactions with actin filaments, could be responsible for the observed association of extra-desmosomal plakophilin-3 with the actin cytoskeleton directly attached to the adherens junctions in A431 epithelial cells. Further, we demonstrate, through lipid binding analyses, that plakophilin-3 can effectively be recruited to the plasma membrane through phosphatidylinositol-4,5-bisphosphate-mediated interactions. Collectively, we report on novel properties of plakophilin-3, which may be conserved throughout the plakophilin protein family and may be behind the roles of these proteins in cell–cell adhesion.  more » « less
Award ID(s):
2232523
PAR ID:
10434248
Author(s) / Creator(s):
; ; ; ; ;
Date Published:
Journal Name:
International Journal of Molecular Sciences
Volume:
24
Issue:
11
ISSN:
1422-0067
Page Range / eLocation ID:
9458
Format(s):
Medium: X
Sponsoring Org:
National Science Foundation
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