Crystal structure of human Acinus RNA recognition motif domain

Area of Science:

• Molecular Biology
• Structural Biology
• Cell Biology

Background:

• Acinus is a nuclear protein essential for apoptosis and RNA splicing.
• It plays a role in chromatin condensation and DNA fragmentation during programmed cell death.
• Activation involves proteolytic cleavage, yielding a truncated p17 form containing the RNA recognition motif (RRM) domain.

Purpose of the Study:

• To determine the crystal structure of the human Acinus RRM domain (AcRRM).
• To elucidate the structural basis for Acinus activation and potential RNA binding.

Main Methods:

• X-ray crystallography was used to determine the structure of the human Acinus RRM domain.
• Resolution of the crystal structure was 1.65 Å.
• Structural comparisons were made with other RRM-RNA complex structures.

Main Results:

• The AcRRM structure exhibits a canonical RRM fold with a four-stranded antiparallel β-sheet and flanking α-helices.
• An additional C-terminal α-helix contains the caspase-3 cleavage site, crucial for Acinus activation.
• This C-terminal helix partially blocks the RNA-binding surface, suggesting a regulatory role in RNA interaction.

Conclusions:

• The crystal structure provides insights into the molecular mechanism of Acinus activation.
• The C-terminal α-helix likely undergoes conformational changes to permit RNA binding post-cleavage.
• This structural understanding is vital for comprehending Acinus function in apoptosis and gene regulation.