Journal article

Structural analysis of phosphorylation-associated interactions of human MCC with Scribble PDZ domains

Sofia Caria, Bryce Z Stewart, Ruitao Jin, Brian J Smith, Patrick O Humbert, Marc Kvansakul

FEBS JOURNAL | WILEY | Published : 2019

Abstract

Scribble is a crucial adaptor protein that plays a pivotal role during establishment and control of cell polarity, impacting many physiological processes ranging from cell migration to immunity and organization of tissue architecture. Scribble harbours a leucine-rich repeat domain and four PDZ domains that mediate most of Scribble's interactions with other proteins. It has become increasingly clear that post-translational modifications substantially impact Scribble-ligand interactions, with phosphorylation being a major modulator of binding to Scribble. To better understand how Scribble PDZ domains direct cell polarity signalling and how phosphorylation impacts this process, we investigated ..

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Grants

Awarded by National Health and Medical Research Council Australia


Awarded by Australian Research Council


Awarded by HPC-GPGPU Facility


Funding Acknowledgements

We thank staff at the MX beamlines, in particular Tom Caradoc-Davis, at the Australian Synchrotron for help with X-ray data collection, and the CSIRO C3 Collaborative Crystallization Centre for assistance with crystallization and the Comprehensive Proteomics Platform at La Trobe University for core instrument support. We thank the ACRF for their support of the Eiger MX detector at the Australian Synchrotron MX2 beamline. This work was supported in whole or part by the National Health and Medical Research Council Australia (Project Grant APP1103871 to MK, POH; Senior Research Fellowship APP1079133 to POH), Australian Research Council (Fellowship FT130101349 to MK) and La Trobe University (Research focus area "Understanding Disease" project grant and Scholarship to BZS). RJ acknowledges receipt of Australian Research Training Scholarships. Part of this work was undertaken using resources from the National Computational Infrastructure, which is supported by the Australian Government and provided through Intersect Australia Ltd, and through the HPC-GPGPU Facility, which was established with the assistance of LIEF Grant LE170100200.