Abstract
| Language | English |
|---|---|
| Pages | 17190-17202 |
| Number of pages | 13 |
| Journal | Journal of Biological Chemistry |
| Volume | 292 |
| Issue number | 42 |
| Early online date | 7 Sep 2017 |
| DOIs | |
| Publication status | Published - 20 Oct 2017 |
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Keywords
- protein-protein interaction
- peptide array
- protein palmitoylation
- cytoskeleton
- ankyrin-repeat domain
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Peptide array–based screening reveals a large number of proteins interacting with the ankyrin-repeat domain of the zDHHC17 S-acyltransferase. / Lemonidis, Kimon; MacLeod, Ruth; Baillie, George S.; Chamberlain, Luke H.
In: Journal of Biological Chemistry, Vol. 292, No. 42, 20.10.2017, p. 17190-17202.Research output: Contribution to journal › Article
TY - JOUR
T1 - Peptide array–based screening reveals a large number of proteins interacting with the ankyrin-repeat domain of the zDHHC17 S-acyltransferase
AU - Lemonidis, Kimon
AU - MacLeod, Ruth
AU - Baillie, George S.
AU - Chamberlain, Luke H.
PY - 2017/10/20
Y1 - 2017/10/20
N2 - 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.
AB - 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.
KW - protein-protein interaction
KW - peptide array
KW - protein palmitoylation
KW - cytoskeleton
KW - ankyrin-repeat domain
UR - http://www.jbc.org/content/early/2017/09/07/jbc.M117.799650
U2 - 10.1074/jbc.M117.799650
DO - 10.1074/jbc.M117.799650
M3 - Article
VL - 292
SP - 17190
EP - 17202
JO - Journal of Biological Chemistry
T2 - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
SN - 0021-9258
IS - 42
ER -