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Title: Structural Basis for Substrate Recognition by the Ankyrin Repeat Domain of Human DHHC17 Palmitoyltransferase

Abstract

DHHC enzymes catalyze palmitoylation, a major post-translational modification that regulates a number of key cellular processes. There are up to 24 DHHCs in mammals and hundreds of substrate proteins that get palmitoylated. However, how DHHC enzymes engage with their substrates is still poorly understood. There is currently no structural information about the interaction between any DHHC enzyme and protein substrates. In this study we have investigated the structural and thermodynamic bases of interaction between the ankyrin repeat domain of human DHHC17 (ANK17) and Snap25b. We solved a high-resolution crystal structure of the complex between ANK17 and a peptide fragment of Snap25b. Through structure-guided mutagenesis, we discovered key residues in DHHC17 that are critically important for interaction with Snap25b. We further extended our finding by showing that the same residues are also crucial for the interaction of DHHC17 with Huntingtin, one of its most physiologically relevant substrates.

Authors:
; ; ;
Publication Date:
Research Org.:
Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
Sponsoring Org.:
National Institutes of Health (NIH)
OSTI Identifier:
1400288
Resource Type:
Journal Article
Resource Relation:
Journal Name: Structure; Journal Volume: 25; Journal Issue: 9
Country of Publication:
United States
Language:
ENGLISH
Subject:
59 BASIC BIOLOGICAL SCIENCES; 60 APPLIED LIFE SCIENCES

Citation Formats

Verardi, Raffaello, Kim, Jin-Sik, Ghirlando, Rodolfo, and Banerjee, Anirban. Structural Basis for Substrate Recognition by the Ankyrin Repeat Domain of Human DHHC17 Palmitoyltransferase. United States: N. p., 2017. Web. doi:10.1016/j.str.2017.06.018.
Verardi, Raffaello, Kim, Jin-Sik, Ghirlando, Rodolfo, & Banerjee, Anirban. Structural Basis for Substrate Recognition by the Ankyrin Repeat Domain of Human DHHC17 Palmitoyltransferase. United States. doi:10.1016/j.str.2017.06.018.
Verardi, Raffaello, Kim, Jin-Sik, Ghirlando, Rodolfo, and Banerjee, Anirban. Fri . "Structural Basis for Substrate Recognition by the Ankyrin Repeat Domain of Human DHHC17 Palmitoyltransferase". United States. doi:10.1016/j.str.2017.06.018.
@article{osti_1400288,
title = {Structural Basis for Substrate Recognition by the Ankyrin Repeat Domain of Human DHHC17 Palmitoyltransferase},
author = {Verardi, Raffaello and Kim, Jin-Sik and Ghirlando, Rodolfo and Banerjee, Anirban},
abstractNote = {DHHC enzymes catalyze palmitoylation, a major post-translational modification that regulates a number of key cellular processes. There are up to 24 DHHCs in mammals and hundreds of substrate proteins that get palmitoylated. However, how DHHC enzymes engage with their substrates is still poorly understood. There is currently no structural information about the interaction between any DHHC enzyme and protein substrates. In this study we have investigated the structural and thermodynamic bases of interaction between the ankyrin repeat domain of human DHHC17 (ANK17) and Snap25b. We solved a high-resolution crystal structure of the complex between ANK17 and a peptide fragment of Snap25b. Through structure-guided mutagenesis, we discovered key residues in DHHC17 that are critically important for interaction with Snap25b. We further extended our finding by showing that the same residues are also crucial for the interaction of DHHC17 with Huntingtin, one of its most physiologically relevant substrates.},
doi = {10.1016/j.str.2017.06.018},
journal = {Structure},
number = 9,
volume = 25,
place = {United States},
year = {Fri Sep 01 00:00:00 EDT 2017},
month = {Fri Sep 01 00:00:00 EDT 2017}
}