Eranthie Weerapana

Eranthie Weerapana

Associate Professor of Chemistry
Boston College
Boston, MA
USA
 617-552-2931
 eranthie@bc.edu

Abstract

Chemical-Proteomic Strategies to Investigate Cysteine Reactivity

Cysteine residues are critical to the catalytic and regulatory functions of diverse proteins including proteases, oxidoreductases and kinases. Although the majority of catalytic cysteine residues within the human proteome are well annotated, the identity and endogenous functions of regulatory cysteines are poorly understood. These regulatory cysteines are often located distal to the catalytic or ligand-binding sites of proteins and typically regulate protein function through posttranslational modifications such as oxidation, nitrosation and lipidation.

To identify and characterize regulatory cysteines, my lab has developed and utilized a suite of chemical-proteomic technologies that report on global changes in cysteine reactivity in vitro and in situ. Several key studies demonstrate the widespread applications of our cysteine reactivity-profiling platforms, including: (1) identifying sites of S-nitrosation in proteomes and characterizing two unannotated S-nitrosation-sensitive cysteine residues on HADH2 and CTSD; (2) developing caged cysteine-reactive probes to identify sites of cysteine oxidation directly in living cells during epidermal growth-factor (EGF) signaling; (3) enriching mitochondria to increase the number of identified mitochondrial cysteines by >10 fold over previous studies; (4) elucidating metal-binding sites on proteins, including cysteine residues involved in zinc and iron coordination; and, (5) characterizing cysteine-mediated protein activities that regulate lifespan through the insulin/IGF-1 signaling pathway. Together, these studies highlight the utility of our chemical-proteomic platforms for elucidating cysteine function in disparate biological systems.

Authors

Eranthie Weerapana

Affiliations

Department of Chemistry, Boston College, Chestnut Hill, MA 02467

Lecture Images

Eranthie Weerapana presenting at APS2019 Eranthie Weerapana presenting at APS2019 Eranthie Weerapana presenting at APS2019