Proteomic identification and structural basis for the interaction between sorting nexin SNX17 and PDLIM family proteins

MD Healy; J Sacharz; KE McNally; C McConville; VA Tillu; RJ Hall; M Chilton; PJ Cullen; M Mobli; R Ghai; DA Stroud; BM Collins

Journal article

Proteomic identification and structural basis for the interaction between sorting nexin SNX17 and PDLIM family proteins

MD Healy, J Sacharz, KE McNally, C McConville, VA Tillu, RJ Hall, M Chilton, PJ Cullen, M Mobli, R Ghai, DA Stroud, BM Collins

Structure | Published : 2022

DOI: 10.1016/j.str.2022.10.001

Abstract

The sorting nexin SNX17 controls endosomal recycling of transmembrane cargo proteins including integrins, the amyloid precursor protein, and lipoprotein receptors. This requires association with the Commander trafficking complex and depends on the C terminus of SNX17 through unknown mechanisms. Using proteomics, we find that the SNX17 C terminus is sufficient for Commander interaction and also associates with members of the PDZ and LIM domain (PDLIM) family. SNX17 contains a type III PDZ binding motif that binds specifically to the PDLIM proteins. The structure of the PDLIM7 PDZ domain bound to the SNX17 C terminus reveals an unconventional perpendicular peptide interaction mediated by elect..

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University of Melbourne Researchers

David Stroud Author

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Grants

Awarded by Lister Institute of Preventive Medicine

Funding Acknowledgements

This work was supported by funds from the National Health and Medical Research Council (NHMRC) to R.G. and D.A.S. (GNT1156732) . M.D.H. is sup-ported by a postgraduate research award from the Australian Institute of Nu-clear Science and Engineering (AINSE; ALNSTU12277) . B.M.C. and D.A.S. are supported by NHMRC fellowships (GNT1136021 to B.M.C.; GNT1140851 to D.A.S.) . M.M. was supported by the Australian Research Council (ARC grant DP190101177) and the NHMRC (GNT1162597) . P.J.C. received funding from the MRC (MR/P018807/1) , Wellcome Trust (104568/Z/14/Z and 220260/Z/20/Z) , Lister Institute of Preventive Medicine, and Royal Society (RSRP/R1/211004) . We would like to thank Barry Thompson for the kind gift of the pcDNA-PDEST47 PDLIM7-GFP plasmid. We thank the Bio21 Mass Spectrometry and Proteomics Facility for the provision of instrumentation. This study made use of the ACRF Cancer Biology Imaging Facilities at the IMB (University of Queensland) .