The structure of the RbBP5 β-propeller domain reveals a surface with potential nucleic acid binding sites

Area of Science:

• Biochemistry
• Molecular Biology
• Epigenetics

Background:

• The WRAD complex (WDR5, RbBP5, Ash2L, Dpy30) is essential for MLL-mediated histone H3K4 methylation.
• RbBP5 plays a key role in MLL catalytic activation and complex targeting to chromatin.
• The WD40 repeat β-propeller domain of RbBP5 was not previously implicated in its catalytic function.

Purpose of the Study:

• To elucidate the structure and function of the RbBP5 β-propeller domain.
• To investigate the role of the RbBP5 β-propeller domain in MLL complex recruitment to chromatin.

Main Methods:

• X-ray crystallography to determine the structure of the RbBP5 β-propeller domain.
• Nuclear Magnetic Resonance (NMR) spectroscopy to analyze binding interactions.

Main Results:

• The structure of the RbBP5 β-propeller domain revealed a unique surface with Arginine clusters.
• NMR data confirmed that the RbBP5 β-propeller domain directly interacts with nucleic acids.
• This interaction suggests a role in recruiting MLL complexes to chromatin targets.

Conclusions:

• The RbBP5 β-propeller domain, beyond its role in catalytic activation, acts as a platform for MLL complex recruitment to chromatin via nucleic acid binding.
• This finding expands our understanding of the WRAD complex's function in epigenetic regulation.