9O6K

Cryo-EM structure of AMT1-AMT7-AMTP1-AMTP2 complex

Summary for 9O6K

• Entry DOI: 10.2210/pdb9o6k/pdb
• EMDB information: 70174
• Descriptor: AMT7, mRNA m(6)A methyltransferase, Myb-like domain-containing protein, ... (5 entities in total)
• Functional Keywords: 6ma methyltransferase, transferase
• Biological source: Tetrahymena thermophila SB210; More
• Total number of polymer chains: 4
• Total formula weight: 153379.55

Authors

Song, J.,Shao, Z. (deposition date: 2025-04-13, release date: 2025-08-13, Last modification date: 2026-02-25)

Primary citation

Shao, Z.,Yoon, S.,Lu, J.,Athavale, P.,Liu, Y.,Song, J.
Structural insight into the substrate binding of the AMT complex via an inhibitor-trapped state.
Protein Sci., 34:e70265-e70265, 2025

PubMed 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.

PubMed: 40815297
DOI: 10.1002/pro.70265

Experimental method

ELECTRON MICROSCOPY (3.59 Å)