Journal article

Crystal structure of the human Scribble PDZ1 domain bound to the PDZ-binding motif of APC

Jing Yuan How, Sofia Caria, Patrick O Humbert, Marc Kvansakul

FEBS LETTERS | WILEY | Published : 2019

Abstract

Scribble (SCRIB) is an important adaptor protein that controls the establishment and maintenance of apico-basal cell polarity. To better understand how SCRIB controls cell polarity signalling via its PDZ domains, we investigated human SCRIB interactions with adenomatous polyposis coli (APC). We show that SCRIB PDZ1, PDZ2 and PDZ3 are the major interactors with the APC PDZ-binding motif (PBM), whereas SCRIB PDZ4 does not show detectable binding to APC. We then determined the crystal structure of SCRIB PDZ1 domain bound to the APC PBM. Our findings reveal a previously unreported pattern of interactions between the SCRIB PDZ domain region with the C-terminal PDZ binding motif of APC, where SCRI..

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Grants

Awarded by National Health and Medical Research Council Australia


Awarded by Australian Research Council


Awarded by La Trobe University


Funding Acknowledgements

We thank staff at the MX beamlines at the Australian Synchrotron for help with X-ray data collection, and the CSIRO C3 Collaborative Crystallization Centre for assistance with crystallisation 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 grant 2000002510).