A quantitative and site-specific atlas of the PADI4-induced citrullinome reveals widespread existence of citrullination
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ABSTRACT: Citrullination refers to the conversion of arginine into the non-essential amino acid citrulline. Despite its importance in physiology and disease, global identification of citrullinated proteins and modification sites has remained challenging. Here, we combined quantitative mass spectrometry-based proteomics with differentiation of a leukemia cell line into neutrophil-like cells to reveal a comprehensive atlas of citrullination sites. Collectively, we identified 14.056 citrullination sites within 4.008 proteins and quantified their regulation in response to PADI4-specific inhibitor GSK484. Hereby we uncovered general principles about the mechanistic and biological aspects of citrullination function, while providing site-specific and quantitative regulation of thousands of PADI4 substrates, including signature histone marks and numerous non-histone events on transcriptional regulators and chromatin-related signaling effectors. Collectively, we describe systems attributes of the human citrullinome, reveal the existence of thousands citrullinated autoantigens in neutrophil cells, and provide a resource framework for investigating PADI4-specific functions and substrates for years to come.
INSTRUMENT(S): Q Exactive HF-X, Orbitrap Exploris 480
ORGANISM(S): Homo Sapiens (human)
TISSUE(S): Neutrophil
DISEASE(S): Rheumatoid Arthritis
SUBMITTER: Alexandra Rebak
LAB HEAD: Michael Lund Nielsen
PROVIDER: PXD038702 | Pride | 2024-01-16
REPOSITORIES: Pride
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