Crystal structure of human Acinus RNA recognition motif domain

Acinus is an abundant nuclear protein involved in apoptosis and splicing. It has been implicated in inducing apoptotic chromatin condensation and DNA fragmentation during programmed cell death. Acinus undergoes activation by proteolytic cleavage that produces a truncated p17 form that comprises only the RNA recognition motif (RRM) domain. We have determined the crystal structure of the human Acinus RRM domain (AcRRM) at 1.65 angstrom resolution. It shows a classical four-stranded antiparallel beta-sheet fold with two flanking alpha-helices and an additional, non-classical alpha-helix at the C-terminus, which harbors the caspase-3 target sequence that is cleaved during Acinus activation. In the structure, the C-terminal alpha-helix partially occludes the potential ligand binding surface of the beta-sheet and hypothetically shields it from non-sequence specific interactions with RNA. Based on the comparison with other RRM-RNA complex structures, it is likely that the C-terminal alpha-helix changes its conformation with respect to the RRM core in order to enable RNA binding by Acinus.