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Related Concept Videos

Protein-protein Interfaces02:04

Protein-protein Interfaces

Many proteins form complexes to carry out their functions, making protein-protein interactions (PPIs) essential for an organism's survival. Most PPIs are stabilized by numerous weak noncovalent chemical forces. The physical shape of the interfaces determines the way two proteins interact. Many globular proteins have closely-matching shapes on their surfaces, which form a large number of weak bonds. Additionally, many PPIs occur between two helices or between a surface cleft and a polypeptide...
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Protein Complexes with Interchangeable Parts

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Conserved Binding Sites01:49

Conserved Binding Sites

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Ligand Binding and Linkage00:49

Ligand Binding and Linkage

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Single-Strand DNA Binding Proteins01:03

Single-Strand DNA Binding Proteins

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Related Experiment Video

Updated: Jul 8, 2026

Single-Molecule Imaging of EWS-FLI1 Condensates Assembling on DNA
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Published on: September 8, 2021

Structural insights into the MLH1-FAN1 interaction reveal an uncharacterized binding interface on MLH1.

Yichang Chen1, Haiyun Hu1, Xinci Shang1

  • 1Jiangsu Key Laboratory of Drug Discovery and Translational Research for Brain Diseases, College of Pharmaceutical Sciences, Soochow University, Suzhou, Jiangsu, China.

Nature Communications
|July 6, 2026
PubMed
Summary

Researchers elucidated the structural basis of the interaction between mismatch repair protein MLH1 and nuclease FAN1, crucial for regulating CAG repeat expansion in Huntington's disease.

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Published on: November 10, 2016

Area of Science:

  • Molecular Biology
  • Genetics
  • Structural Biology

Background:

  • Huntington's disease pathogenesis involves CAG repeat expansion in the mutant huntingtin gene.
  • Nuclease FAN1 and mismatch repair protein MLH1 interact to regulate this expansion, but the structural details are unknown.

Purpose of the Study:

  • To determine the structural basis of the interaction between human MLH1 and nuclease FAN1.
  • To provide a structural framework for understanding the regulation of CAG repeat expansion.

Main Methods:

  • Co-immunoprecipitation assays to confirm protein interactions in cells.
  • X-ray crystallography to determine the structures of MLH1-FAN1 complexes.
  • Analysis of MLH1-FAN1 binding affinities using FAN1-derived peptides.

Main Results:

  • The MLH1 C-terminal domain binds FAN1-derived MIP and MIM motifs with similar affinities.
  • Crystal structures revealed conserved MLH1-MIP recognition and a novel S3 binding site for MLH1-MIM.
  • Mutating key MLH1 residues disrupted FAN1 binding in cellular assays.

Conclusions:

  • Established the molecular basis for MLH1-FAN1 recognition.
  • Identified novel binding interactions and sites between MLH1 and FAN1.
  • Provided structural insights into the regulation of CAG repeat expansion in Huntington's disease.