Related Experiment Video

Updated: Jan 27, 2026

Peptide-based Identification of Functional Motifs and their Binding Partners
14:28

Peptide-based Identification of Functional Motifs and their Binding Partners

Published on: June 30, 2013

13.0K

A tryptophan-phenylalanine binding motif for the histone methyltransferases MLL4 and MLL3

Soumi Biswas1, Zohreh Tavaf1, Caroline Benz2

  • 1Department of Pharmacology, University of Colorado School of Medicine, Aurora, Colorado, USA.

The Journal of Biological Chemistry
|January 25, 2026
PubMed

Insights

Researchers discovered a specific tryptophan-phenylalanine binding motif recognized by human methyltransferases mixed lineage leukemia 4 (MLL4) and 3 (MLL3). This finding reveals a new interaction mechanism potentially linking MLL4/MLL3 to epigenetic regulation in cancer.

Area of Science:

  • Epigenetics and Molecular Biology
  • Protein-Protein Interactions
  • Cancer Biology

Background:

  • Mixed lineage leukemia 4 (MLL4) and 3 (MLL3) are human methyltransferases crucial for epigenetic and transcriptional regulation.
  • Understanding the molecular mechanisms of MLL4 and MLL3 function is key to deciphering their roles in cellular processes and disease.

Purpose of the Study:

  • To identify and characterize novel binding motifs recognized by MLL4 and MLL3.
  • To elucidate the molecular basis of the interaction between MLL4/MLL3 and identified motifs.
  • To explore the potential role of this interaction in oncogenic transcriptional programs.

Main Methods:

  • Proteomic peptide-phage screening of intrinsically disordered regions of the human proteome.
  • Nuclear Magnetic Resonance (NMR) and MicroScale Thermophoresis (MST) assays for binding confirmation.
  • Mutational, genetic, and binding interface analyses to determine the interaction mechanism.

Main Results:

  • Identification and characterization of a tryptophan-phenylalanine binding motif recognized by MLL4 and MLL3.
  • Confirmation of binding between the sixth PHD finger of MLL4 and the seventh PHD finger of MLL3 with the motif.
  • Demonstration of a high correlation between MLL4/MLL3 expression and motif-containing proteins in various tumor types.

Conclusions:

  • The study reveals a direct interaction mechanism between MLL4/MLL3 and a specific tryptophan-phenylalanine motif.
  • This interaction suggests a potential link between MLL4/MLL3 methyltransferases and motif-containing epigenetic coregulators in cancer.
  • The findings open new avenues for understanding MLL4/MLL3-mediated transcriptional control in both normal and pathological contexts.
Keywords:
KMT2MLL3MLL4PHD fingerinteractionmotif

More Related Videos

Antibody-Free Assay for RNA Methyltransferase Activity Analysis08:31

Antibody-Free Assay for RNA Methyltransferase Activity Analysis

Published on: July 9, 2019

7.6K
Profiling of Methyltransferases and Other S-adenosyl-L-homocysteine-binding Proteins by Capture Compound Mass Spectrometry CCMS17:12

Profiling of Methyltransferases and Other S-adenosyl-L-homocysteine-binding Proteins by Capture Compound Mass Spectrometry CCMS

Published on: December 20, 2010

16.0K

Related Concept Videos

Histone Modification02:32

Histone Modification

The histone proteins have a flexible N-terminal tail extending out from the nucleosome. These histone tails are often subjected to post-translational modifications such as acetylation, methylation, phosphorylation, and ubiquitination. Particular combinations of these modifications form “histone codes” that influence the chromatin folding and tissue-specific gene expression.
Acetylation
The enzyme histone acetyltransferase adds acetyl group to the histones. Another enzyme, histone...
16.0K
Histone Modification02:32

Histone Modification

4.4K
Conserved Binding Sites01:49

Conserved Binding Sites

Many proteins’ biological role depends on their interactions with their ligands, small molecules that bind to specific locations on the protein known as ligand-binding sites. Ligand-binding sites are often conserved among homologous proteins as these sites are critical for protein function.
Binding sites are often located in large pockets, and if their location on a protein’s surface is unknown, it can be predicted using various approaches. The energetic method computationally...
5.1K
Histone Variants at the Centromere02:30

Histone Variants at the Centromere

Histone variants are the histone proteins with structural and sequence variations. These variants may be regarded as “mutant” forms that replace their canonical histone counterparts in the nucleosomes. Specific post-translational modifications on the histone variants enable further chromatin complexity and regulate tissue-specific gene expression. The most common histone variants are from histone H2A, H2B, and linker histone H1 families. However, several variants of histone H3...
5.0K
Cooperative Binding of Transcription Regulators02:13

Cooperative Binding of Transcription Regulators

Transcriptional regulators bind to specific cis-regulatory sequences in the DNA to regulate gene transcription. These cis-regulatory sequences are very short, usually less than ten nucleotide pairs in length. The short length means that there is a high probability of the exact same sequence randomly occurring throughout the genome.  Since regulators can also bind to groups of similar sequences, this further increases the chances of random binding. Transcriptional regulators form...
7.2K
The Equilibrium Binding Constant and Binding Strength02:18

The Equilibrium Binding Constant and Binding Strength

The equilibrium binding constant (Kb) quantifies the strength of a protein-ligand interaction. Kb can be calculated as follows when the reaction is at equilibrium:
14.9K