Seminar

Graduate Student Jeffrey Julien

Thursday, March 10, 2022 - 10:45am
Neville 3

"In vitro Post-Translational Modifications of Caveolin-1 and its Effect on Protein Structure, Topology, and Oligomerization in Model Membranes"

The importance of understanding membrane protein structure and function is growing after scientists have recognized that approximately one third of the human genome encodes for membrane proteins.1 Caveolin-1, an integral membrane protein, is found within caveolae, which are 50 − 100 nm bulbous invaginations of the plasma membrane. Importantly, caveolin-1 is responsible for caveolae biogenesis and coordinates a host of cellular processes.2 Alterations in cellular levels of the caveolin protein, along with mutant forms, have been implicated in a variety of disease states including cancer, heart disease, muscular dystrophy, and Alzheimer’s Disease.2 While there is a large body of work documenting the cellular behavior of caveolin in both normal and disease states, there are key perplexities pertaining to its atomic-level structure that remain enigmatic.3 For example, there is a lack of studies probing the effects of palmitoylation on caveolin-1 structure and function. To bridge this gap, I will present our recent progress on the development of a methodology in which caveolin-1 can be reliably and selectively palmitoylated in vitro, which has and will allow us to address the effect of palmitoylation on the structure, topology, and oligomerization of caveolin-1 in model membranes.4–6

(1) Overington, J. P.; Al-Lazikani, B.; Hopkins, A. L. How Many Drug Targets Are There? Nat. Rev. Drug Discov. 2006, 5 (12), 993–996.

(2) Parton, R. G. Caveolae: Structure, Function, and Relationship to Disease. Annu. Rev. Cell Dev. Biol. 2018, 34 (1), 111–136.

(3) Root, K. T.; Plucinsky, S. M.; Glover, K. J. Recent Progress in the Topology, Structure, and Oligomerization of Caveolin: A Building Block of Caveolae. Curr. Top. Membr. 2015, 75, 305–336.

(4) Julien, J. A.; Fernandez, M. G.; Brandmier, K. M.; Del Mundo, J. T.; Bator, C. M.; Loftus, L. A.; Gomez, E. W.; Gomez, E. D.; Glover, K. J. Rapid Preparation of Nanodiscs for Biophysical Studies. Arch. Biochem. Biophys. 2021, 109051.

(5) Julien, J. A.; Mutchek, S. G.; Fernandez, M. G.; Glover, K. J. Facile Production of Tagless Membrane Scaffold Protein for Nanodiscs. Anal. Biochem. 2022, 638, 114497.

(6) Julien, J. A.; Perone, T. V.; LaGatta, D. M.; Hong, C.; Park, S.; Fuanta, R.; Im, W.; Glover, K. J. One-Step Site Specific S-Alkylation of Full-Length Caveolin-1: Lipidation Modulates Membrane Depth but Not Helicity of Its C-Terminal Domain. Manuscript in preparation.