title: Detection and identification of protein citrullination in complex biological systems.
abstract: Protein citrullination is a post-translational modification of arginine that is catalyzed by the Protein Arginine Deiminase (PAD) family of enzymes. Aberrantly increased citrullination is associated with a host of inflammatory diseases and cancer and PAD inhibitors have shown remarkable efficacy in a range of diseases including rheumatoid arthritis, lupus, atherosclerosis, and ulcerative colitis. In rheumatoid arthritis, citrullinated proteins serve as key antigens for rheumatoid arthritis-associated autoantibodies. These data suggest that citrullinated proteins may serve more generally as biomarkers of specific disease states, however, the identification of citrullinated residues remains challenging due to the small 1Da mass change that occurs upon citrullination. Herein, we highlight the available techniques to identify citrullinated proteins/residues focusing on advanced MS techniques as well as chemical derivatization strategies that are currently being employed to identify citrullinated proteins as well as the specific residues modified within those proteins.
authors.affiliation: Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, 364 Plantation St., Worcester, MA 10605, United States; Program in Chemical Biology, University of Massachusetts Medical School, 364 Plantation St., Worcester, MA 10605, United States; Oncology Discovery Eli Lilly and Company, Indianapolis, IN 46285, United States.
authors.forename: Kathleen W
authors.initials: KW
authors.lastname: Clancy
authors.affiliation: Department of Chemistry, Boston College, 2609 Beacon St., Chestnut Hill, MA 02467, United States.
authors.forename: Eranthie
authors.initials: E
authors.lastname: Weerapana
authors.affiliation: Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, 364 Plantation St., Worcester, MA 10605, United States; Program in Chemical Biology, University of Massachusetts Medical School, 364 Plantation St., Worcester, MA 10605, United States. Electronic address: paul.thompson@umassmed.edu.
authors.forename: Paul R
authors.initials: PR
authors.lastname: Thompson
mesh_terms: D000818:Animals; D001120:Arginine / Q000378:metabolism*; D002956:Citrulline / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D013058:Mass Spectrometry; D011499:Protein Processing, Post-Translational; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D011506:Proteins; D002956:Citrulline; D001120:Arginine