Independent Researcher CONICET / Adjunct Professor UNC
Phone: +54 351 5353855 ext 3420
Protein S-acylation in yeast
S-acylation of proteins, commonly known as palmitoylation, is a widespread post-translational modification that consist in the addition of a lipid molecule to a cysteine residue of a protein through a thioesther bond. This modification is of great relevance in important biological processes such as signal transduction and synaptic transmission and it is therefore linked to a variety of disorders of the nervous system and to cancer processes. Our main aim is to acquire detailed knowledge of the process of S-acylation; the mechanism, the enzymes responsible and the functional consequences of this modification, with particular emphasis in how it affects proteins transit to different organelles or membrane domains. As an experimental model, we use the yeast Saccharomyces cerevisiae. Palmitoylation is mediated by a family of proteins characterized by the presence of a domain of about 50 amino acids, rich in cysteine called DHHC-CRD (Cysteine-Rich Domain) We focus on the palmitoyltransferase Swf1, that is responsible for palmitoylation of transmembrane proteins called SNARES involved in membrane fusion. Additionally, we try to identify inhibitors of mammalian and parasites PATs, by chemical-genetic strategies in yeast, in order to test their potential therapeutic properties.
- Slow diffusion of proteins in the yeast plasma membrane allows polarity to be maintained by endocytic cycling. Valdez-Taubas J, Pelham HR. Current Biology (2003), 13(18), 1636-1640.
- Swf1-dependent palmitoylation of the SNARE Tlg1 prevents its ubiquitination and degradation. Valdez-Taubas J and Pelham H. The EMBO Journal (2005), 24(14), 2524-2532
- A novel motif at the C-terminus of palmitoyltransferases is essential for Swf1 and Pfa3 function in vivo. González Montoro, Quiroga R, Maccioni HJF and Valdez Taubas J*. Biochem J. 2009 Apr 15;419(2):301-8.
- Short transmembrane domains with high volume exoplasmic halves determine retention of type II membrane proteins in the Golgi complex. Quiroga R, A Trenchi, González Montoro, Valdez Taubas J*, and Maccioni HJF* The Journal of Cell Science (2013) 126 :5344-5349. *Co-authors corresponding
- Zinc coordination by the DHHC cystein-rich domain of the palmitoyltransferase Swf1. González Montoro, Quiroga R and Valdez Taubas J, Biochem. J. (2013) 454 (427–43)
- PIP CONICET 2011. Role of the transmembrane domain and S-acylation in the subcelullar lozalization of membrane of membrane proteins in eucaryotic cells””. to Dres H Maccioni, J.L Daniotti y J. Valdez Taube . AR $ 180.000.
- PICT 2013 0288 Role of the transmembrane domain and S-acylation in the subcellular localization of membrane proteins. "AR $ 420000. three years
- Industrial Chemistry Institute-technician "El Obraje" .High Gracia, Córdoba, Argentina; December 1989.
- “BSC honours degree” in Biological Chemistry, Faculty of Chemical Sciences, National University of Cordoba, Argentina; September 1994.
- “PhD in Chemical Sciences”, Faculty of Chemical Sciences, National University of Cordoba, Argentina; September, 1999. Subject “Molecular Biology of Purine transporters in Aspergillus nidulans”
Dr. Javier Valdez Taubas, graduated in 1994 as BSC in Chemistry at the School of Chemical Sciences, National University of Cordoba (UNC). He carried-out his doctoral thesis under the direction of Dr. Alberto Rosa in CIQUIBIC-Department of Biological Chemistry, at the School of Chemical Sciences, UNC (1995-1999), studying purine permeases of the filamentous fungus Aspergillus nidulans.This work was partly carried out in collaboration with Dr. Claudio Scazzocchio University of Paris-Sud, France. After his thesis, he stayed briefly in the laboratory of Dr. Monique Bolotin in Paris to learn basic techniques to work with the yeast Saccharomyces cerevisiae, and then joined the laboratory of Dr. Hugo Maccioni in CIQUIBIC for a short period of post-doctoral training (2000-2002). There he tried to apply the genetic tools available in yeast to study how Golgi glycolipid-glycosyltranferasas (GGTs) attain their localization in this organelle. In early 2002, he obtained a postdoctoral position in the laboratory led by Dr. Hugh Pelham in the Laboratory of Molecular Biology MRC (Medical Research Council), in Cambridge, UK, to study intracellular traffic of membrane proteins in yeast. During this period, he determined that a protein called Swf1 is involved in palmitoylation of transmembrane proteins, in cysteine residues that are close or even within their transmembrane domains.
He returned to Córdoba in late 2005, where he joined the group of Dr. Hugo Maccioni as a research assistant. Initially he worked in projects underway in the laboratory and then returned to the study of the Palmitoyltransferase Swf1, which has been the focus of his research since 2007. In 2008, as a research associate his first student joined the group. At this stage, a new protein motif present in most palmitoyl (PATs) which is essential for its function was described. More recently they showed for the first time that the DHHC domain in PATs, it is a zinc-binding domain and binding to this metal has a structural and not a catalytic role.
In 2014, he was promoted to independent researcher and now continues with studies of structure-function in PATs, and also they are trying to identify and characterize the Swf1 orthologue in mammals.
PATs have been proposed as interesting therapeutic targets for their action on numerous signalling proteins. He recently started another line of research to find specific inhibitors of PATs from different origins using by chemical-genetic strategies in yeast
Dr. Valdez Taubas is an assistant professor at the School of Chemical Sciences, National University of Cordoba since 2008 with teaching roles in the Cellular and Molecular Biology course. Additionally, he participates in teaching a posgraduate course in yeast genetics, has co-organised several post-graduate courses in membrane traffic and also a course in yeast systems biology. Institutional Management Background He has been a member of the directive board of the School of Chemical Sciences, a member of the directive board of CIQUIBIC, and currently serves as Director of the Department of Biological Chemistry.
Directed Ph.D. Theses
2013- Dr. Montoro Gonzalez Ayelén, “Structure-function analyses of yeast S-acyltransferasaes”