5K7U

Crystal structure of the catalytic domains of Mettl3/Mettl14 complex with SAM

Summary for 5K7U

• Entry DOI: 10.2210/pdb5k7u/pdb
• Related: 5K7M 5K7W
• Descriptor: N6-adenosine-methyltransferase 70 kDa subunit, N6-adenosine-methyltransferase subunit METTL14, S-ADENOSYLMETHIONINE, ... (4 entities in total)
• Functional Keywords: methyltransferase, methyladenosine, m6a, transferase
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 2
• Total formula weight: 65704.64

Authors

Wang, P.,Doxtader, K.A.,Nam, Y. (deposition date: 2016-05-26, release date: 2016-07-06, Last modification date: 2024-02-28)

Primary citation

Wang, P.,Doxtader, K.A.,Nam, Y.
Structural Basis for Cooperative Function of Mettl3 and Mettl14 Methyltransferases.
Mol.Cell, 63:306-317, 2016

PubMed Abstract: N(6)-methyladenosine (m(6)A) is a prevalent, reversible chemical modification of functional RNAs and is important for central events in biology. The core m(6)A writers are Mettl3 and Mettl14, which both contain methyltransferase domains. How Mettl3 and Mettl14 cooperate to catalyze methylation of adenosines has remained elusive. We present crystal structures of the complex of Mettl3/Mettl14 methyltransferase domains in apo form as well as with bound S-adenosylmethionine (SAM) or S-adenosylhomocysteine (SAH) in the catalytic site. We determine that the heterodimeric complex of methyltransferase domains, combined with CCCH motifs, constitutes the minimally required regions for creating m(6)A modifications in vitro. We also show that Mettl3 is the catalytically active subunit, while Mettl14 plays a structural role critical for substrate recognition. Our model provides a molecular explanation for why certain mutations of Mettl3 and Mettl14 lead to impaired function of the methyltransferase complex.

PubMed: 27373337
DOI: 10.1016/j.molcel.2016.05.041

Experimental method

X-RAY DIFFRACTION (1.7 Å)