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Updated: Jun 5, 2026
09:35
Resolving Affinity Purified Protein Complexes by Blue Native PAGE and Protein Correlation Profiling
Published on: April 1, 2017
Structural and biochemical insights into MLL1 core complex assembly.
Vanja Avdic1, Pamela Zhang, Sylvain Lanouette
1Ottawa Institute of Systems Biology, Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, ON K1H 8M5, Canada.
Structure (London, England : 1993)
|January 12, 2011
Summary
This study reveals how RbBP5 connects Ash2L and WDR5, detailing the WDR5-RbBP5 interaction critical for MLL1 methyltransferase activity and complex assembly.
Area of Science:
- Molecular Biology
- Structural Biology
- Biochemistry
Background:
- Histone H3 Lys-4 methylation is crucial for gene regulation and is catalyzed by methyltransferases.
- These methyltransferases require a complex of WDR5, RbBP5, and Ash2L for enzymatic activity.
Purpose of the Study:
- To elucidate the structural basis of the WDR5-RbBP5 subcomplex formation.
- To understand the role of RbBP5-WDR5 interactions in MLL1 methyltransferase activity.
Main Methods:
- X-ray crystallography to determine the structure of WDR5 in complex with RbBP5 and MLL1.
- Mutational analyses of WDR5 and RbBP5 to assess the importance of their interactions.
Main Results:
- A 50-residue segment of RbBP5 bridges the Ash2L C-terminal domain to WDR5.
- Crystal structure shows RbBP5 and MLL1 binding to opposite sides of WDR5's beta-propeller domain.
- RbBP5 interacts with a V-shaped cleft on WDR5 via hydrogen bonds and van der Waals contacts.
- Mutations disrupting RbBP5-WDR5 interactions impair MLL1 methyltransferase activity.
Conclusions:
- The study provides the structural foundation for WDR5-RbBP5 subcomplex assembly.
- WDR5 plays a critical role in scaffolding the MLL1 core complex, essential for histone methylation.
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