Director’s guest: Javier Cifuente, Biofisika Institute, Spain – “Structural Basis of Human ER Protein O-Glycosylation:  Enzyme Function Mechanisms and Its Implication in Congenital Diseases”

Abstract

Protein glycosylation is essential for mammalian development, and defects in glycosyltransferases cause a range of congenital disorders. Mammalian O-mannosylation remains poorly understood despite its biological and clinical importance. This talk describes the structural basis of endoplasmic reticulum (ER) glycosyltransferase that drives a novel O-mannosylation pathway involved in congenital disorders of glycosylation. Cryo–electron microscopy structures captured in substrate-bound states reveal how this enzyme engages its sugar donor and protein acceptors to catalyze sugar transfer. The structures explain acceptor specificity and show how this enzyme acts on protein substrates. Present findings provide a molecular framework for understanding its links to developmental disease.

Biography

Javier Cifuente received a degree in Biochemistry from the Universidad Nacional de La Plata, Argentina, where he also completed his Ph.D. on viral pathogenesis under the supervision of Dr. Ricardo Gomez. He subsequently moved to the United States to conduct postdoctoral research on the structural basis of virus-host interactions with Prof. Susan Hafenstein at Penn State University. He relocated to Europe to investigate structural enzymology with Prof. Marcelo Guerin at several institutions in Spain, including the University of the Basque Country, CIC bioGUNE, and BioCruces. He is currently a postdoctoral researcher in Prof. Iban Ubarretxena’s laboratory at the Biofisika Institute in Spain, where he leads research on membrane proteins involved in the pathogenesis of congenital diseases. His primary research interests included elucidating the structural basis of pathogenesis and exploring structure-function relationships from an evolutionary perspective.