Evidence map›Paper›PMID 42409804›Full record

ArticleNature communications2026

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

Yichang Chen, Haiyun Hu, Xinci Shang, Keri M Fishwick, Giada Greco, Qin Xiao, Yinhao Zhou, Qiuyan Huang, Tao Jiang, Xiaolei Huang and 6 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

16 authors.

Yichang Chen *Jiangsu Key Laboratory of Drug Discovery and Translational Research for Brain Diseases, College of Pharmaceutical Sciences, Soochow University, Suzhou, Jiangsu, China.
Haiyun Hu *Jiangsu Key Laboratory of Drug Discovery and Translational Research for Brain Diseases, College of Pharmaceutical Sciences, Soochow University, Suzhou, Jiangsu, China.ORCID http://orcid.org/0009-0009-0088-6052
Xinci Shang *Jiangsu Key Laboratory of Drug Discovery and Translational Research for Brain Diseases, College of Pharmaceutical Sciences, Soochow University, Suzhou, Jiangsu, China.
Keri M FishwickInstitute of Molecular Cancer Research, University of Zurich, Zurich, Switzerland.
Giada GrecoInstitute of Molecular Cancer Research, University of Zurich, Zurich, Switzerland.
Qin XiaoJiangsu Key Laboratory of Drug Discovery and Translational Research for Brain Diseases, College of Pharmaceutical Sciences, Soochow University, Suzhou, Jiangsu, China.
Yinhao ZhouJiangsu Key Laboratory of Drug Discovery and Translational Research for Brain Diseases, College of Pharmaceutical Sciences, Soochow University, Suzhou, Jiangsu, China.
Qiuyan HuangJiangsu Key Laboratory of Drug Discovery and Translational Research for Brain Diseases, College of Pharmaceutical Sciences, Soochow University, Suzhou, Jiangsu, China.
Tao JiangJiangsu Key Laboratory of Drug Discovery and Translational Research for Brain Diseases, College of Pharmaceutical Sciences, Soochow University, Suzhou, Jiangsu, China.
Xiaolei HuangJiangsu Key Laboratory of Drug Discovery and Translational Research for Brain Diseases, College of Pharmaceutical Sciences, Soochow University, Suzhou, Jiangsu, China.
Guanghui WangJiangsu Key Laboratory of Drug Discovery and Translational Research for Brain Diseases, College of Pharmaceutical Sciences, Soochow University, Suzhou, Jiangsu, China.ORCID http://orcid.org/0000-0001-8551-6468
Xuechu ZhenJiangsu Key Laboratory of Drug Discovery and Translational Research for Brain Diseases, College of Pharmaceutical Sciences, Soochow University, Suzhou, Jiangsu, China.ORCID http://orcid.org/0000-0001-7458-2566
Guoqiang XuJiangsu Key Laboratory of Drug Discovery and Translational Research for Brain Diseases, College of Pharmaceutical Sciences, Soochow University, Suzhou, Jiangsu, China.ORCID http://orcid.org/0000-0002-4753-4769
Su QinLife Science Research Center, Southern University of Science and Technology, Guangdong, China.
Alessandro A SartoriInstitute of Molecular Cancer Research, University of Zurich, Zurich, Switzerland.ORCID http://orcid.org/0000-0003-2770-0333
Yanli LiuJiangsu Key Laboratory of Drug Discovery and Translational Research for Brain Diseases, College of Pharmaceutical Sciences, Soochow University, Suzhou, Jiangsu, China. ylliu18@suda.edu.cn.ORCID http://orcid.org/0000-0003-0197-7617

Funding

National Natural Science Foundation of China (National Science Foundation of China) 32271309
6 · The paper itself

Abstract

Huntington's disease is driven by CAG repeat expansion in the mutant huntingtin gene. Nuclease FAN1 and mismatch repair protein MLH1 regulate repeat expansion through direct interaction, but the underlying structural basis remains unclear. Here, we show that the MLH1 C-terminal domain binds to FAN1-derived peptides containing either the MIP or MIM motif with comparable affinities. Crystal structures of this domain bound to each motif provide structural insights into human MLH1-FAN1 interaction, revealing a conserved mechanism for FAN1-MIP recognition and a previously unrecognized binding site on MLH1, termed the S3 site, for FAN1-MIM engagement. Co-immunoprecipitation assays confirmed that mutation of key MLH1 residues disrupts FAN1 binding in cells. These findings establish the molecular basis of MLH1-FAN1 recognition and provide a structural framework for understanding the regulation of CAG repeat expansion in Huntington's disease.

Indexed as

ExodeoxyribonucleasesMultifunctional EnzymesMutL Protein Homolog 1Binding SitesCrystallography, X-RayEndodeoxyribonucleasesHumansHuntington DiseaseModels, MolecularProtein BindingProtein DomainsEndodeoxyribonucleasesExodeoxyribonucleasesFAN1 protein, humanMLH1 protein, humanMultifunctional EnzymesMutL Protein Homolog 1

Identifiers

PMID42409804
PMCPMC13473659

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.