Structural basis of nucleosome deubiquitination by the bidentate Calypso/ASX complex

Unexpectedly, only one Calypso/ASX copy engages the nucleosomal substrate in a conformation analogous to that observed in human BAP1/ASXL1, while the second unit remains structurally disengaged. We further identify the C-terminal tail of Calypso as the principal determinant of substrate affinity through direct interaction with nucleosomal DNA.

Together, these findings support a model in which the bidentate Calypso/ASX complex enables processive deubiquitination along chromatin through alternating or cooperative catalytic engagement.