Structural insight into the function of human peptidyl arginine deiminase 6

• DOI: 10.1016/j.csbj.2024.08.019
• Publication Date: 2024-08-16T23:37:16Z
• Authors: Jack P.C. Williams; Stephane Mouilleron; Rolando Hernandez...; M. Teresa Bertran; Joseph A. Marsh; Louise J. Walport
• Keywords: Arginine deiminase; Conserved sequence

Peptidyl arginine deiminase 6 (PADI6 or PAD6) is vital for early embryonic development in mice and humans, yet its function remains elusive. PADI6 less conserved than other PADIs it currently unknown whether has a catalytic function. Here we show that human dimerises like hPADIs 2–4, however, does not bind Ca2+ inactive vitro assays against standard PADI substrates. By determining the crystal structure of hPADI6, hPADI6 structured absence where hPADI2 hPADI4 are not, Ca-binding sites conserved. Moreover, whilst key aspartic acid histidine residues structurally conserved, cysteine displaced far from active site centre pocket appears closed through unique evolved mechanism present PADIs. Taken together, these findings provide insight into how may differ based on provides resource characterising damaging effect clinically significant variants.Graphical abstract