24-26 November 2021
Online
Australia/Sydney timezone

Structural basis of the Trichoplax adhaerens Scribble and Dlg interactions with the PDZ-binding motif of Vangl

25 Nov 2021, 17:42
1m
Online

Online

Poster Biomedicine, Life science & Food Science Poster Session

Speaker

Mrs Janesha Maddumage (1Department of Biochemistry and Genetics, La Trobe University)

Description

Maintenance of multicellular tissue architecture is conserved process which is regulated by a highly
conserved set of proteins. The interacting partners of these regulators are also conserved across the
animal kingdom. Scribble and Dlg are two such key polarity regulators that involve in the establishment
and maintenance of multicellular apical-basal cell polarity in epithelial cells. These are scaffolding
proteins bearing multiple PDZ domains that mediate most of their interactions. Complex multicellular
organisms evolved from the simple primitive forms; therefore, we examined Scribble and Dlg mediated
cell polarity in the simplest metazoan living on earth, Placazoa, Trichoplax adhaerens. Despite its
extreme simplicity, Trichoplax contains all polarity regulators that are fundamental to instruct the body
plans in higher animals; thus, making it an ideal candidate to use as a polarity studying model. We now
show biochemically that a key interaction for the establishment of cell polarity between Scribble and
Dlg PDZ domains and Vangl in mammals is fully recapitulated in Trichoplax. We found that Scribble
PDZ1, PDZ2 and PDZ3 interact with Vangl with affinities comparable to the human interaction, with
a similar hierarchy in affinities. We also found that all three PDZ domains of Dlg interact with Vangl
with no hierarchy of their affinities. We then show using crystal structures of Scribble PDZ1, PDZ2 and
Dlg PDZ1, PDZ2 bound to the C-terminal PDZ binding motif of Vangl that in addition to the binding
affinities, the detailed interactions between Scribble/Vangl and Dlg/Vangl are also conserved at the
atomic level between Trichoplax and human.

Which facility did you use for your research Australian Synchrotron
Presenter Gender Woman
Level of Expertise Student
Condition of submission Yes
Students Only - Are you interested in AINSE student funding Yes
Do you wish to take part in the Student Poster Slam Yes

Primary authors

Mrs Janesha Maddumage (1Department of Biochemistry and Genetics, La Trobe University) Prof. Marc Kvansakul (Department of Biochemistry and Genetics, La Trobe University; Research Centre for Molecular Cancer Prevention, La Trobe University) Prof. Humbert Patrick (1Department of Biochemistry and Genetics, La Trobe University, Melbourne, Victoria 3086, Australia; Research Centre for Molecular Cancer Prevention, La Trobe University, Melbourne, Victoria 3086, Australia ;Department of Biochemistry & Molecular Biology, University of Melbourne, Melbourne, Victoria 3010, Australia; Department of Clinical Pathology, University of Melbourne, Melbourne, Victoria 3010, Australia)

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