Related Experiment Video
Updated: Feb 25, 2026

Optimized Incorporation of Alkynyl Fatty Acid Analogs for the Detection of Fatty Acylated Proteins using Click Chemistry
Published on: April 9, 2021
Structural Basis for Substrate Recognition by the Ankyrin Repeat Domain of Human DHHC17 Palmitoyltransferase
Raffaello Verardi1, Jin-Sik Kim1, Rodolfo Ghirlando2
1Unit on Structural and Chemical Biology of Membrane Proteins, Cell Biology and Neurobiology Branch, National Institute of Child Health and Human Development, National Institutes of Health, 35A Convent Drive, Bethesda, MD 20892, USA.
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.
Related Concept Videos
Lipids as Anchors
The carboxy-terminal of most of the prenylated proteins, such as Ras proteins, contains...
Mitochondrial Precursor Proteins
Most of the mitochondrial...
Allosteric Proteins-ATCase
Aspartate transcarbamoylase (ATCase) is a cytosolic enzyme that catalyzes the condensation of L-aspartate and carbamoyl phosphate to N-carbamoyl-L-aspartate. This reaction is the first step in pyrimidine biosynthesis. UTP and CTP, the end products of the pyrimidine synthesis...
Tail-anchoring of Proteins in the ER Membrane
The ADP/ATP Carrier Protein
Conserved Binding Sites
Binding sites are often located in large pockets, and if their location on a protein’s surface is unknown, it can be predicted using various approaches. The energetic method computationally...

