A quantitative and site-specific atlas of the citrullinome reveals widespread existence of citrullination and insights into PADI4 substrates

Research output: Contribution to journal › Journal article › Research › peer-review

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A quantitative and site-specific atlas of the citrullinome reveals widespread existence of citrullination and insights into PADI4 substrates. / Rebak, Alexandra S.; Hendriks, Ivo A.; Elsborg, Jonas D.; Buch-Larsen, Sara C.; Nielsen, Claus H.; Terslev, Lene; Kirsch, Rebecca; Damgaard, Dres; Doncheva, Nadezhda T.; Lennartsson, Caroline; Rykær, Martin; Jensen, Lars J.; Christophorou, Maria A.; Nielsen, Michael L.

In: Nature Structural and Molecular Biology, 2024.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Rebak, AS, Hendriks, IA, Elsborg, JD, Buch-Larsen, SC, Nielsen, CH, Terslev, L, Kirsch, R, Damgaard, D, Doncheva, NT, Lennartsson, C, Rykær, M, Jensen, LJ, Christophorou, MA & Nielsen, ML 2024, 'A quantitative and site-specific atlas of the citrullinome reveals widespread existence of citrullination and insights into PADI4 substrates', Nature Structural and Molecular Biology. https://doi.org/10.1038/s41594-024-01214-9

APA

Rebak, A. S., Hendriks, I. A., Elsborg, J. D., Buch-Larsen, S. C., Nielsen, C. H., Terslev, L., Kirsch, R., Damgaard, D., Doncheva, N. T., Lennartsson, C., Rykær, M., Jensen, L. J., Christophorou, M. A., & Nielsen, M. L. (2024). A quantitative and site-specific atlas of the citrullinome reveals widespread existence of citrullination and insights into PADI4 substrates. Nature Structural and Molecular Biology. https://doi.org/10.1038/s41594-024-01214-9

Vancouver

Rebak AS, Hendriks IA, Elsborg JD, Buch-Larsen SC, Nielsen CH, Terslev L et al. A quantitative and site-specific atlas of the citrullinome reveals widespread existence of citrullination and insights into PADI4 substrates. Nature Structural and Molecular Biology. 2024. https://doi.org/10.1038/s41594-024-01214-9

Author

Rebak, Alexandra S. ; Hendriks, Ivo A. ; Elsborg, Jonas D. ; Buch-Larsen, Sara C. ; Nielsen, Claus H. ; Terslev, Lene ; Kirsch, Rebecca ; Damgaard, Dres ; Doncheva, Nadezhda T. ; Lennartsson, Caroline ; Rykær, Martin ; Jensen, Lars J. ; Christophorou, Maria A. ; Nielsen, Michael L. / A quantitative and site-specific atlas of the citrullinome reveals widespread existence of citrullination and insights into PADI4 substrates. In: Nature Structural and Molecular Biology. 2024.

Bibtex

@article{7724d5575d6a47738076914083fb283a,
title = "A quantitative and site-specific atlas of the citrullinome reveals widespread existence of citrullination and insights into PADI4 substrates",
abstract = "Despite the importance of citrullination in physiology and disease, global identification of citrullinated proteins, and the precise targeted sites, has remained challenging. Here we employed quantitative-mass-spectrometry-based proteomics to generate a comprehensive atlas of citrullination sites within the HL60 leukemia cell line following differentiation into neutrophil-like cells. We identified 14,056 citrullination sites within 4,008 proteins and quantified their regulation upon inhibition of the citrullinating enzyme PADI4. With this resource, we provide quantitative and site-specific information on thousands of PADI4 substrates, including signature histone marks and transcriptional regulators. Additionally, using peptide microarrays, we demonstrate the potential clinical relevance of certain identified sites, through distinct reactivities of antibodies contained in synovial fluid from anti-CCP-positive and anti-CCP-negative people with rheumatoid arthritis. Collectively, we describe the human citrullinome at a systems-wide level, provide a resource for understanding citrullination at the mechanistic level and link the identified targeted sites to rheumatoid arthritis.",
author = "Rebak, {Alexandra S.} and Hendriks, {Ivo A.} and Elsborg, {Jonas D.} and Buch-Larsen, {Sara C.} and Nielsen, {Claus H.} and Lene Terslev and Rebecca Kirsch and Dres Damgaard and Doncheva, {Nadezhda T.} and Caroline Lennartsson and Martin Ryk{\ae}r and Jensen, {Lars J.} and Christophorou, {Maria A.} and Nielsen, {Michael L.}",
note = "Publisher Copyright: {\textcopyright} The Author(s) 2024.",
year = "2024",
doi = "10.1038/s41594-024-01214-9",
language = "English",
journal = "Nature Structural and Molecular Biology",
issn = "1545-9993",
publisher = "nature publishing group",

}

RIS

TY - JOUR

T1 - A quantitative and site-specific atlas of the citrullinome reveals widespread existence of citrullination and insights into PADI4 substrates

AU - Rebak, Alexandra S.

AU - Hendriks, Ivo A.

AU - Elsborg, Jonas D.

AU - Buch-Larsen, Sara C.

AU - Nielsen, Claus H.

AU - Terslev, Lene

AU - Kirsch, Rebecca

AU - Damgaard, Dres

AU - Doncheva, Nadezhda T.

AU - Lennartsson, Caroline

AU - Rykær, Martin

AU - Jensen, Lars J.

AU - Christophorou, Maria A.

AU - Nielsen, Michael L.

N1 - Publisher Copyright: © The Author(s) 2024.

PY - 2024

Y1 - 2024

N2 - Despite the importance of citrullination in physiology and disease, global identification of citrullinated proteins, and the precise targeted sites, has remained challenging. Here we employed quantitative-mass-spectrometry-based proteomics to generate a comprehensive atlas of citrullination sites within the HL60 leukemia cell line following differentiation into neutrophil-like cells. We identified 14,056 citrullination sites within 4,008 proteins and quantified their regulation upon inhibition of the citrullinating enzyme PADI4. With this resource, we provide quantitative and site-specific information on thousands of PADI4 substrates, including signature histone marks and transcriptional regulators. Additionally, using peptide microarrays, we demonstrate the potential clinical relevance of certain identified sites, through distinct reactivities of antibodies contained in synovial fluid from anti-CCP-positive and anti-CCP-negative people with rheumatoid arthritis. Collectively, we describe the human citrullinome at a systems-wide level, provide a resource for understanding citrullination at the mechanistic level and link the identified targeted sites to rheumatoid arthritis.

AB - Despite the importance of citrullination in physiology and disease, global identification of citrullinated proteins, and the precise targeted sites, has remained challenging. Here we employed quantitative-mass-spectrometry-based proteomics to generate a comprehensive atlas of citrullination sites within the HL60 leukemia cell line following differentiation into neutrophil-like cells. We identified 14,056 citrullination sites within 4,008 proteins and quantified their regulation upon inhibition of the citrullinating enzyme PADI4. With this resource, we provide quantitative and site-specific information on thousands of PADI4 substrates, including signature histone marks and transcriptional regulators. Additionally, using peptide microarrays, we demonstrate the potential clinical relevance of certain identified sites, through distinct reactivities of antibodies contained in synovial fluid from anti-CCP-positive and anti-CCP-negative people with rheumatoid arthritis. Collectively, we describe the human citrullinome at a systems-wide level, provide a resource for understanding citrullination at the mechanistic level and link the identified targeted sites to rheumatoid arthritis.

U2 - 10.1038/s41594-024-01214-9

DO - 10.1038/s41594-024-01214-9

M3 - Journal article

C2 - 38321148

AN - SCOPUS:85184233102

JO - Nature Structural and Molecular Biology

JF - Nature Structural and Molecular Biology

SN - 1545-9993

ER -

ID: 383092251