5L6E

Crystal structure of the human METTL3-METTL14 complex bound to SAM

Summary for 5L6E

• Entry DOI: 10.2210/pdb5l6e/pdb
• Descriptor: N6-adenosine-methyltransferase 70 kDa subunit, N6-adenosine-methyltransferase subunit METTL14, S-ADENOSYLMETHIONINE, ... (6 entities in total)
• Functional Keywords: methyltransferase n6-adenine methylation m6a rossmann fold, transferase
• Biological source: Homo sapiens (Human); More
• Cellular location: Nucleus : Q86U44 Q9HCE5
• Total number of polymer chains: 2
• Total formula weight: 59858.48

Authors

Sledz, P.,Jinek, M. (deposition date: 2016-05-29, release date: 2016-10-12, Last modification date: 2024-01-10)

Primary citation

Sledz, P.,Jinek, M.
Structural insights into the molecular mechanism of the m(6)A writer complex.
Elife, 5:-, 2016

PubMed Abstract: Methylation of adenosines at the N(6) position (m(6)A) is a dynamic and abundant epitranscriptomic mark that regulates critical aspects of eukaryotic RNA metabolism in numerous biological processes. The RNA methyltransferases METTL3 and METTL14 are components of a multisubunit m(6)A writer complex whose enzymatic activity is substantially higher than the activities of METTL3 or METTL14 alone. The molecular mechanism underpinning this synergistic effect is poorly understood. Here we report the crystal structure of the catalytic core of the human m(6)A writer complex comprising METTL3 and METTL14. The structure reveals the heterodimeric architecture of the complex and donor substrate binding by METTL3. Structure-guided mutagenesis indicates that METTL3 is the catalytic subunit of the complex, whereas METTL14 has a degenerate active site and plays non-catalytic roles in maintaining complex integrity and substrate RNA binding. These studies illuminate the molecular mechanism and evolutionary history of eukaryotic m(6)A modification in post-transcriptional genome regulation.

PubMed: 27627798
DOI: 10.7554/eLife.18434

Experimental method

X-RAY DIFFRACTION (1.901 Å)