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Sci Signal. 2018 Feb 13;11(517). pii: eaam9899. doi: 10.1126/scisignal.aam9899.

Structural basis for the interaction between the cell polarity proteins Par3 and Par6.

Author information

1
Max Planck Institute for Developmental Biology, Max-Planck-Ring 5, 72076 Tübingen, Germany.
2
Molecular and Cellular Anatomy, University of Regensburg, Universitätsstrasse 31, 93053 Regensburg, Germany.
3
Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, 600 University Avenue, Toronto, Ontario M5G 1X5, Canada.
4
Medical Clinic D, University Hospital of Münster, Domagkstraβe 3a, 48149 Münster, Germany.
5
Max Planck Institute for Developmental Biology, Max-Planck-Ring 5, 72076 Tübingen, Germany. silke.wiesner@ur.de.

Abstract

Polarity is a fundamental property of most cell types. The Par protein complex is a major driving force in generating asymmetrically localized protein networks and consists of atypical protein kinase C (aPKC), Par3, and Par6. Dysfunction of this complex causes developmental abnormalities and diseases such as cancer. We identified a PDZ domain-binding motif in Par6 that was essential for its interaction with Par3 in vitro and for Par3-mediated membrane localization of Par6 in cultured cells. In fly embryos, we observed that the PDZ domain-binding motif was functionally redundant with the PDZ domain in targeting Par6 to the cortex of epithelial cells. Our structural analyses by x-ray crystallography and NMR spectroscopy showed that both the PDZ1 and PDZ3 domains but not the PDZ2 domain in Par3 engaged in a canonical interaction with the PDZ domain-binding motif in Par6. Par3 thus has the potential to recruit two Par6 proteins simultaneously, which may facilitate the assembly of polarity protein networks through multivalent PDZ domain interactions.

PMID:
29440511
DOI:
10.1126/scisignal.aam9899

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