| Structural highlights
5w7j is a 4 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Gene: | ZDHHC17, HIP14, HIP3, HYPH, KIAA0946, HSPC294 (HUMAN) |
| Activity: | Protein S-acyltransferase, with EC number 2.3.1.225 |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
[ZDH17_HUMAN] Palmitoyltransferase specific for a subset of neuronal proteins, including SNAP25, DLG4/PSD95, GAD2, SYT1 and HD. Palmitoylates MPP1 in erythrocytes. May be involved in the sorting or targeting of critical proteins involved in the initiating events of endocytosis at the plasma membrane. Has transforming activity. Mediates Mg(2+) transport.[1] [2] [3] [4] [5]
Publication Abstract from PubMed
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.
Structural Basis for Substrate Recognition by the Ankyrin Repeat Domain of Human DHHC17 Palmitoyltransferase.,Verardi R, Kim JS, Ghirlando R, Banerjee A Structure. 2017 Jul 18. pii: S0969-2126(17)30214-9. doi:, 10.1016/j.str.2017.06.018. PMID:28757145[6]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Singaraja RR, Hadano S, Metzler M, Givan S, Wellington CL, Warby S, Yanai A, Gutekunst CA, Leavitt BR, Yi H, Fichter K, Gan L, McCutcheon K, Chopra V, Michel J, Hersch SM, Ikeda JE, Hayden MR. HIP14, a novel ankyrin domain-containing protein, links huntingtin to intracellular trafficking and endocytosis. Hum Mol Genet. 2002 Nov 1;11(23):2815-28. PMID:12393793
- ↑ Huang K, Yanai A, Kang R, Arstikaitis P, Singaraja RR, Metzler M, Mullard A, Haigh B, Gauthier-Campbell C, Gutekunst CA, Hayden MR, El-Husseini A. Huntingtin-interacting protein HIP14 is a palmitoyl transferase involved in palmitoylation and trafficking of multiple neuronal proteins. Neuron. 2004 Dec 16;44(6):977-86. PMID:15603740 doi:http://dx.doi.org/S0896627304007500
- ↑ Ducker CE, Stettler EM, French KJ, Upson JJ, Smith CD. Huntingtin interacting protein 14 is an oncogenic human protein: palmitoyl acyltransferase. Oncogene. 2004 Dec 9;23(57):9230-7. PMID:15489887 doi:http://dx.doi.org/10.1038/sj.onc.1208171
- ↑ Goytain A, Hines RM, Quamme GA. Huntingtin-interacting proteins, HIP14 and HIP14L, mediate dual functions, palmitoyl acyltransferase and Mg2+ transport. J Biol Chem. 2008 Nov 28;283(48):33365-74. doi: 10.1074/jbc.M801469200. Epub 2008, Sep 15. PMID:18794299 doi:http://dx.doi.org/10.1074/jbc.M801469200
- ↑ Lach A, Grzybek M, Heger E, Korycka J, Wolny M, Kubiak J, Kolondra A, Boguslawska DM, Augoff K, Majkowski M, Podkalicka J, Kaczor J, Stefanko A, Kuliczkowski K, Sikorski AF. Palmitoylation of MPP1 (membrane-palmitoylated protein 1)/p55 is crucial for lateral membrane organization in erythroid cells. J Biol Chem. 2012 Jun 1;287(23):18974-84. doi: 10.1074/jbc.M111.332981. Epub 2012, Apr 10. PMID:22496366 doi:http://dx.doi.org/10.1074/jbc.M111.332981
- ↑ Verardi R, Kim JS, Ghirlando R, Banerjee A. Structural Basis for Substrate Recognition by the Ankyrin Repeat Domain of Human DHHC17 Palmitoyltransferase. Structure. 2017 Jul 18. pii: S0969-2126(17)30214-9. doi:, 10.1016/j.str.2017.06.018. PMID:28757145 doi:http://dx.doi.org/10.1016/j.str.2017.06.018
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