Evidence map›Paper›PMID 40815297›Full record

ArticleProtein science : a publication of the Protein Society2025

Structural insight into the substrate binding of the AMT complex via an inhibitor-trapped state.

Zengyu Shao, Sol Yoon, Jiuwei Lu, Pranav Athavale, Yifan Liu, Jikui Song

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PubMed Full text at PMC Publisher
In one paragraph

Article in Protein science : a publication of the Protein Society, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. Article
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

6 authors.

Zengyu ShaoDepartment of Biochemistry, University of California, Riverside, California, USA.
Sol YoonDepartment of Biochemistry, University of California, Riverside, California, USA.
Jiuwei LuDepartment of Biochemistry, University of California, Riverside, California, USA.
Pranav AthavaleDepartment of Biochemistry, University of California, Riverside, California, USA.
Yifan LiuDepartment of Cancer Biology, University of Southern California, Los Angeles, California, USA.
Jikui SongDepartment of Biochemistry, University of California, Riverside, California, USA.ORCID 0000-0002-4958-1032

Funding

NCCAT: National Center for CryoEM Access and Training- Supplement for Windows 10 and FFIU24GM129539 · NIGMS · NEW YORK STRUCTURAL BIOLOGY CENTER · PI DE MARCO, ALEX, KIEFT, JEFFREY S · 2018 to 2023
$53.9M
Mechanistic Insights into Mammalian DNA MethylationR35GM119721 · NIGMS · UNIVERSITY OF CALIFORNIA RIVERSIDE · PI Jikui Song · 2016 to 2026
$5.3M
National Science Foundation MCB-2435178NIGMS NIH HHS R35 GM119721NIGMS NIH HHS U24 GM129539NIH HHS R35GM119721
6 · The paper itself

Abstract

N6-adenine (6mA) DNA methylation plays an important role in gene regulation and genome stability. The 6mA methylation in Tetrahymena thermophila is mainly mediated by the AMT complex, comprised of the AMT1, AMT7, AMTP1, and AMTP2 subunits. To date, how this complex assembles on the DNA substrate remains elusive. Here we report the structure of the AMT complex bound to the OCR protein from bacteriophage T7, mimicking the AMT-DNA encounter complex. The AMT1-AMT7 heterodimer approaches OCR from one side, while the AMTP1 N-terminal domain, assuming a homeodomain fold, binds to OCR from the other side, resulting in a saddle-shaped architecture reminiscent of what was observed for prokaryotic 6mA writers. Mutation of the AMT1, AMT7, and AMTP1 residues on the OCR-contact points led to impaired DNA methylation activity to various extents, supporting a role for these residues in DNA binding. Furthermore, structural comparison of the AMT1-AMT7 subunits with the evolutionarily related METTL3-METTL14 and AMT1-AMT6 complexes reveals sequence conservation and divergence in the region corresponding to the OCR-binding site, shedding light on the substrate binding of the latter two complexes. Together, this study supports a model in which the AMT complex undergoes a substrate binding-induced open-to-closed conformational transition, with implications in its substrate binding and processive 6mA methylation.

Indexed as

Bacteriophage T7Protozoan ProteinsTetrahymena thermophilaCrystallography, X-RayDNA MethylationModels, MolecularProtein BindingProtozoan Proteins6mA DNA methylationAMT complexDNA methyltransferaseenzyme–substrate recognitionhomeodomainmaintenance DNA methylationopen‐to‐close conformational transitionprotein–DNA interaction

Identifiers

PMID40815297
PMCPMC12355966

What Socratic holds

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Registered trials

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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 Socratic graph.