Peptide array–based screening reveals a large number of proteins interacting with the ankyrin-repeat domain of the zDHHC17 S-acyltransferase

Lemonidis, Kimon and MacLeod, Ruth and Baillie, George S. and Chamberlain, Luke H. (2017) Peptide array–based screening reveals a large number of proteins interacting with the ankyrin-repeat domain of the zDHHC17 S-acyltransferase. Journal of Biological Chemistry, 292 (42). pp. 17190-17202. ISSN 1083-351X

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    Abstract

    zDHHC S-acyl-transferases are enzymes catalyzing protein S-acylation, a common post-translational modification on proteins frequently affecting their membrane targeting and trafficking. The ankyrin-repeat (AR) domain of zDHHC17 (HIP14) and zDHHC13 (HIP14L) S-acyltransferases, which is involved in both substrate recruitment and S-acylation-independent functions, was recently shown to bind at least six proteins, by specific recognition of a consensus sequence in them. To further refine the rules governing binding to the AR of zDHHC17, we employed peptide arrays based on zDHHC AR-binding motif (zDABM) sequences of synaptosomal-associated protein 25 (SNAP25) and cysteine string protein alpha (CSPα). Quantitative comparisons of the binding preferences of 400 peptides allowed us to construct a position-specific scoring matrix (PSSM) for zDHHC17 AR binding, with which we predicted and subsequently validated many putative zDHHC17 interactors. We identified 95 human zDABM sequences with unexpected versatility in amino-acid usage; these sequences were distributed among 90 proteins, of which 62 have not been previously implicated in zDHHC17/13 binding. These zDABM-containing proteins included all family members of the SNAP25, sprouty, cornifelin, ankyrin, and SLAIN-motif containing families; seven endogenous Gag polyproteins sharing the same binding sequence; and several proteins involved in cytoskeletal organization, cell communication, and regulation of signaling. A dozen of the zDABM-containing proteins had more than one zDABM sequence, while isoform-specific binding to the AR of zDHHC17 was identified for the Ena/VASP-like protein. The large number of zDABM sequences within the human proteome suggests that zDHHC17 may be an interaction hub regulating many cellular processes.

    Creators(s): Lemonidis, Kimon ORCID logoORCID: https://orcid.org/0000-0003-1332-6002, MacLeod, Ruth, Baillie, George S. and Chamberlain, Luke H. ORCID logoORCID: https://orcid.org/0000-0002-8701-4995;
    Item type:Article
    ID code:61995
    Keywords:protein-protein interaction, peptide array, protein palmitoylation, cytoskeleton, ankyrin-repeat domain, Pharmacy and materia medica, Biochemistry, Cell Biology, Molecular Biology
    Subjects:Medicine > Pharmacy and materia medica
    Department:Faculty of Science > Strathclyde Institute of Pharmacy and Biomedical Sciences
    Depositing user: Pure Administrator
    Date deposited:11 Oct 2017 10:21
    Last modified:21 Jan 2021 09:33
    Related URLs:
    URI:https://strathprints.strath.ac.uk/id/eprint/61995
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