Premium
Human peptidylarginine deiminase types 2 and 4 target glycine‐containing motifs for citrullination: An in silico study
Author(s) -
Olson Justin Scott,
Meyer Dylan,
Grant Jennifer
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.lb82
Subject(s) - citrullination , arginine , in silico , citrulline , biochemistry , protein secondary structure , chemistry , peptide , peptide sequence , protein structure , computational biology , amino acid , biology , gene
The human peptidyl arginine deiminases (hPAD), a family of five calcium‐dependent enzymes, facilitates the post‐translational modification, citrullination. The isozymes hPAD2 and hPAD4 are of particular importance, as they appear to play a role in the development and progression of several autoimmune diseases. To better characterize primary and secondary structure determinants of citrullination, we mined protein sequences known to contain arginine residues susceptible to citrullination by hPAD2 or hPAD4 from the literature, generating protein secondary structure predictions using PSIPRED prediction software. Of the citrullinated sequences identified, 70% of citrullinated arginine for hPAD2 and 81% of citrullinated arginine for hPAD4 were predicted to reside within a disordered secondary structure. The motif extracting software Motif‐X was used to elucidate statistically significant motifs within the general peptide data sets and within a data set of peptides belonging to disordered secondary structure conformations. Both hPAD2 and hPAD4 appear to favor citrullination of motifs containing arginine neighbored by glycine at the +1 and/or +2 position, and hPAD4 favors glycine the +3 position, relative to the target arginine.