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

被引:30
|
作者
Lemonidis, Kimon [1 ]
MacLeod, Ruth [2 ]
Baillie, George S. [2 ]
Chamberlain, Luke H. [1 ]
机构
[1] Univ Strathclyde, Strathclyde Inst Pharm & Biomed Sci, 161 Cathedral St, Glasgow G4 0RE, Lanark, Scotland
[2] Univ Glasgow, Inst Cardiovasc & Med Sci, Wolfson Link Bldg, Glasgow G12 8QQ, Lanark, Scotland
基金
英国生物技术与生命科学研究理事会;
关键词
MAP KINASE ACTIVATION; PALMITOYL ACYLTRANSFERASE; SUBSTRATE RECOGNITION; STRUCTURAL BASIS; HUNTINGTONS-DISEASE; MEMBRANE SUPPORTS; HIP14; DIFFERENTIATION; CELLS; MICE;
D O I
10.1074/jbc.M117.799650
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
zDHHC S-acyltransferases 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 onz DHHCAR-binding motif(zDABM) sequences of synaptosom-al-associated protein 25 (SNAP25) and cysteine string protein alpha (CSP alpha). 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, whereas 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.
引用
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页码:17190 / 17202
页数:13
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