Citrullination: new tricks for an old mod

Christophorou, Maria A.; Sharma, Priyanka; Zhang, Xuesen

doi:10.1098/rstb.2022.0235

Cited by 1 publication

(1 citation statement)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Members of the peptidyl arginine deiminase (PADI) family catalyze post-translational calcium-dependent citrullination of arginines, converting them into the non-coded amino acid citrulline [1][2][3][4]. Arginine citrullination is a widespread post-translational modification (PTM) that increases the hydrophobicity of proteins and can contribute to fine-tuning physiological processes.…”

Section: Introductionmentioning

confidence: 99%

Evolutionary analysis reveals the role of a non-catalytic domain of peptidyl arginine deiminase 2 in transcriptional regulation

Villanueva‐Cañas

Fernández-Fuentes

Teyssier

et al. 2022

Preprint

Self Cite

View full text Add to dashboard Cite

Protein citrullination (deimination) is the post-translational modification of arginine to the non-coded amino acid citrulline and is catalyzed by the peptidyl arginine deiminase (PADI) enzyme family. The most widely expressed of the PADIs family, PADI2, regulates cellular processes that impact several diseases. How PADI2 has evolved in mammals to gain its fundamental function is not fully understood. By performing a systematic evolutionary analysis, we now identify 20 positively selected residues in PADI2, 16 of which are structurally exposed mainly on the N-terminal and middle domains of PADI2. Our integrated evolutionary and structural analyses suggest that these residues have roles in maintaining the PADI2 interactions with cognate proteins. We experimentally demonstrate that one of the loops in the middle domain participates in the interactions of PADI2 with the positive-transcription elongation factor (P-TEFb), which is essential for active transcription and cellular proliferation. This interpretation is supported by our finding that L162 within this loop evolved under positive selection. Our work demonstrates the power of combining sequence-based phylogenetic methods with structural information for investigating the selective function of the middle domain of PADI2 in modulating transcription. This in-depth knowledge could be key to understanding the role of PADI2 overexpression in disease and points to potential targetable regions of the protein.

show abstract

Section: Introductionmentioning

confidence: 99%