5IL0

Crystal structural of the METTL3-METTL14 complex for N6-adenosine methylation

Summary for 5IL0

• Entry DOI: 10.2210/pdb5il0/pdb
• Related: 5IL1 5IL2
• Descriptor: METTL3, METTL14, 1,2-ETHANEDIOL, ... (5 entities in total)
• Functional Keywords: methyltransferase, rna binding protein
• Biological source: Homo sapiens (Human); More
• Cellular location: Nucleus : Q86U44 Q9HCE5
• Total number of polymer chains: 2
• Total formula weight: 59425.55

Authors

Wang, X.,Guan, Z.,Zou, T.,Yin, P. (deposition date: 2016-03-04, release date: 2016-05-25, Last modification date: 2024-11-06)

Primary citation

Wang, X.,Feng, J.,Xue, Y.,Guan, Z.,Zhang, D.,Liu, Z.,Gong, Z.,Wang, Q.,Huang, J.,Tang, C.,Zou, T.,Yin, P.
Structural basis of N6-adenosine methylation by the METTL3-METTL14 complex
Nature, 534:575-578, 2016

PubMed Abstract: Chemical modifications of RNA have essential roles in a vast range of cellular processes. N(6)-methyladenosine (m(6)A) is an abundant internal modification in messenger RNA and long non-coding RNA that can be dynamically added and removed by RNA methyltransferases (MTases) and demethylases, respectively. An MTase complex comprising methyltransferase-like 3 (METTL3) and methyltransferase-like 14 (METTL14) efficiently catalyses methyl group transfer. In contrast to the well-studied DNA MTase, the exact roles of these two RNA MTases in the complex remain to be elucidated. Here we report the crystal structures of the METTL3-METTL14 heterodimer with MTase domains in the ligand-free, S-adenosyl methionine (AdoMet)-bound and S-adenosyl homocysteine (AdoHcy)-bound states, with resolutions of 1.9, 1.71 and 1.61 Å, respectively. Both METTL3 and METTL14 adopt a class I MTase fold and they interact with each other via an extensive hydrogen bonding network, generating a positively charged groove. Notably, AdoMet was observed in only the METTL3 pocket and not in METTL14. Combined with biochemical analysis, these results suggest that in the m(6)A MTase complex, METTL3 primarily functions as the catalytic core, while METTL14 serves as an RNA-binding platform, reminiscent of the target recognition domain of DNA N(6)-adenine MTase. This structural information provides an important framework for the functional investigation of m(6)A.

PubMed: 27281194
DOI: 10.1038/nature18298

Experimental method

X-RAY DIFFRACTION (1.882 Å)