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Structural and Biochemical Insights into MLL1 Core Complex Assembly
- Source :
- Structure. 19(1):101-108
- Publication Year :
- 2011
- Publisher :
- Elsevier BV, 2011.
-
Abstract
- SummaryHistone H3 Lys-4 methylation is predominantly catalyzed by a family of methyltransferases whose enzymatic activity depends on their interaction with a three-subunit complex composed of WDR5, RbBP5, and Ash2L. Here, we report that a segment of 50 residues of RbBP5 bridges the Ash2L C-terminal domain to WDR5. The crystal structure of WDR5 in ternary complex with RbBP5 and MLL1 reveals that both proteins binds peptide-binding clefts located on opposite sides of WDR5′s β-propeller domain. RbBP5 engages in several hydrogen bonds and van der Waals contacts within a V-shaped cleft formed by the junction of two blades on WDR5. Mutational analyses of both the WDR5 V-shaped cleft and RbBP5 residues reveal that the interactions between RbBP5 and WDR5 are important for the stimulation of MLL1 methyltransferase activity. Overall, this study provides the structural basis underlying the formation of the WDR5-RbBP5 subcomplex and further highlight the crucial role of WDR5 in scaffolding the MLL1 core complex.
- Subjects :
- Methyltransferase
Stereochemistry
Recombinant Fusion Proteins
Amino Acid Motifs
Molecular Sequence Data
Sequence alignment
Plasma protein binding
03 medical and health sciences
Histone H3
0302 clinical medicine
Protein structure
Structural Biology
Humans
Protein Interaction Domains and Motifs
Amino Acid Sequence
Protein Structure, Quaternary
Ternary complex
Molecular Biology
030304 developmental biology
0303 health sciences
biology
Chemistry
Intracellular Signaling Peptides and Proteins
Nuclear Proteins
Methylation
Histone-Lysine N-Methyltransferase
3. Good health
Protein Structure, Tertiary
DNA-Binding Proteins
Histone
030220 oncology & carcinogenesis
biology.protein
Protein Multimerization
Sequence Alignment
Myeloid-Lymphoid Leukemia Protein
Protein Binding
Subjects
Details
- ISSN :
- 09692126
- Volume :
- 19
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Structure
- Accession number :
- edsair.doi.dedup.....51b5d4c05f5ebdc839e70b6f3952f52e
- Full Text :
- https://doi.org/10.1016/j.str.2010.09.022