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A quantitative and site-specific atlas of the PADI4-induced citrullinome reveals widespread existence of citrullination

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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			Action	DRS
	20191209_QE6_LC6_AS_SA_DMSO_Cal15_F10_R2.raw	Raw
	20191209_QE6_LC6_AS_SA_DMSO_Cal15_F10_R3.raw	Raw
	20191209_QE6_LC6_AS_SA_DMSO_Cal15_F10_R4.raw	Raw
	20191209_QE6_LC6_AS_SA_DMSO_Cal15_F11_R2.raw	Raw
	20191209_QE6_LC6_AS_SA_DMSO_Cal15_F11_R3.raw	Raw

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