Protein Prenylation - The Anchor of Life
Protein prenylation is a post-translational modification that consists of the attachment of 15 or 20 carbon isoprenoids to specific cysteine residues positioned near the C-termini of proteins. In a eukaryotic cell, there are several hundred prenylated proteins including most members of the Ras superfamily and heterotrimeric G-proteins; the prenyl group serves to anchor these proteins in the membrane so that they are positioned to interact with cell surface receptors either directly or via adaptor proteins. This means that essentially all signaling processes in eukaryotic cells require the participation of prenylated proteins for everything ranging from the regulation of cell division to stem cell differentiation and development. Beyond biological significance, the critical role of prenylated proteins also makes them important targets for the design of new therapeutic agents for a variety of diseases.
Research in the Distefano Group
Works in the Distefano Group on protein prenylation is focused in two areas: Chemical Biology and Biotechnology Applications. In pursuit of those studies, members of the group perform a variety of different types of experiments including chemical synthesis, biochemistry, proteomics, cell culture and animal-based work. The goal of these works is to gain insight into protein prenylation that can be used to advance biology and develop new therapeutic approaches for a broad range of diseases including cancer, Alzheimer’s disease and infectious disease.
Research Highlights
MDD Group News
Pa Thao Presents Research at the 2019 Pathways to Research Program Symposium
Undergraduate Pa Thao presented her work on "Exploring the differences among statins on enhancing metabolic and in vitro labeling of prenylated proteins using isoprenoid probes" at the 2019 Pathways to Research Program Symposium. This summer program allowed Pa to focus full time over the summer on this project. She and graduate student mentor Kiall Suazo are in the process of assembling a manuscript that reports the results of this work for publication.
Group Members Attend FASEB Conference on Protein Lipid Modification
Distefano group members Mina Ahmadi, Shelby Auger, Taysir Bader and Kiall Suazo attended the 2019 FASEB conference on protein lipid modification. This biannual international conference, similar to a Gordon Research Conference, was attended by 86 scientists, physicians, students and fellows from the US and 8 other countries including Canada, China, France, Germany, Great Britain, Poland, Singapore, and Switzerland. This conference allowed an international group of scientists working on protein lipid modification to meet and discuss research in the field for an entire week on the campus of a small college in upstate New York without the distractions associated with a larger urban setting. The scientific presentations reported new discoveries related to the biology of protein lipid modification and how that biology is relevant to a variety of diseases including cancer, Alzheimer’s disease and fungal infections. Recent results from efforts in drug discovery by academic and industrial scientists who attended the meeting were also presented highlighting the importance of this conference for translational research. Discussion among the attendees resulted in the establishment of new collaborations. Mina, Taysir, Shelby and Kiall all presented posters and Taysir won an award for best poster.
Metabolic labeling with alkyne analogue yields functional proteins
In a recent article published in Bioconjugate Chemistry, graduate student Veronica Diaz-Rodriguez and undergraduate Elena Werst, in the research group of Mark Distefano, in collaboration with Erh-Ting Hsu and Professor Christine Hrycyna at Purdue University and Dr. Elena Ganusova and Professor Jeff Becker at the University of Tennessee demonstrate that a‑Factor Analogues Containing Alkyne- and Azide-Functionalized Isoprenoids Are Efficiently Enzymatically Processed and Retain Wild- Type Bioactivity.