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SUMMARY:Structural basis of the Trichoplax adhaerens Scribble and Dlg inte
 ractions with the PDZ-binding motif of Vangl
DTSTART:20211125T064200Z
DTEND:20211125T064300Z
DTSTAMP:20261007T033300Z
UID:indico-contribution-4203@events.synchrotron.org.au
DESCRIPTION:Speakers: Marc Kvansakul (Department of Biochemistry and Genet
 ics\, La Trobe University\; Research Centre for Molecular Cancer Preventio
 n\, La Trobe University)\, Janesha Maddumage (1Department of Biochemistry 
 and Genetics\, La Trobe University)\, Humbert Patrick  (1Department of Bio
 chemistry and Genetics\, La Trobe University\, Melbourne\, Victoria 3086\,
  Australia\; Research Centre for Molecular Cancer Prevention\, La Trobe Un
 iversity\, Melbourne\, Victoria 3086\, Australia \;Department of Biochemis
 try & Molecular Biology\, University of Melbourne\, Melbourne\, Victoria 3
 010\, Australia\; Department of Clinical Pathology\, University of Melbour
 ne\, Melbourne\, Victoria 3010\, Australia)\n\nMaintenance of multicellula
 r tissue architecture is conserved process which is regulated by a highly\
 nconserved set of proteins. The interacting partners of these regulators a
 re also conserved across the\nanimal kingdom. Scribble and Dlg are two suc
 h key polarity regulators that involve in the establishment\nand maintenan
 ce of multicellular apical-basal cell polarity in epithelial cells. These 
 are scaffolding\nproteins bearing multiple PDZ domains that mediate most o
 f their interactions. Complex multicellular\norganisms evolved from the si
 mple primitive forms\; therefore\, we examined Scribble and Dlg mediated\n
 cell polarity in the simplest metazoan living on earth\, Placazoa\, Tricho
 plax adhaerens. Despite its\nextreme simplicity\, Trichoplax contains all 
 polarity regulators that are fundamental to instruct the body\nplans in hi
 gher animals\; thus\, making it an ideal candidate to use as a polarity st
 udying model. We now\nshow biochemically that a key interaction for the es
 tablishment of cell polarity between Scribble and\nDlg PDZ domains and Van
 gl in mammals is fully recapitulated in Trichoplax. We found that Scribble
 \nPDZ1\, PDZ2 and PDZ3 interact with Vangl with affinities comparable to t
 he human interaction\, with\na similar hierarchy in affinities. We also fo
 und that all three PDZ domains of Dlg interact with Vangl\nwith no hierarc
 hy of their affinities. We then show using crystal structures of Scribble 
 PDZ1\, PDZ2 and\nDlg PDZ1\, PDZ2 bound to the C-terminal PDZ binding motif
  of Vangl that in addition to the binding\naffinities\, the detailed inter
 actions between Scribble/Vangl and Dlg/Vangl are also conserved at the\nat
 omic level between Trichoplax and human.\n\nhttps://events.synchrotron.org
 .au/event/146/contributions/4203/
LOCATION:Online
RELATED-TO:indico-event-146@events.synchrotron.org.au
URL:https://events.synchrotron.org.au/event/146/contributions/4203/
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