5WCJ

Crystal Structure of Human Methyltransferase-like protein 13 in complex with SAH

Summary for 5WCJ

• Entry DOI: 10.2210/pdb5wcj/pdb
• Descriptor: Methyltransferase-like protein 13, UNKNOWN ATOM OR ION, S-ADENOSYL-L-HOMOCYSTEINE, ... (4 entities in total)
• Functional Keywords: methyltransferase, rossman fold, sah-binding, sgc, structural genomics, structural genomics consortium, transferase
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 1
• Total formula weight: 27924.41

Authors

Halabelian, L.,Loppnau, P.,Seitova, A.,Hutchinson, A.,Hunt, B.,Dong, A.,Bountra, C.,Edwards, A.M.,Arrowsmith, C.H.,Structural Genomics Consortium (SGC) (deposition date: 2017-06-30, release date: 2017-07-19, Last modification date: 2023-10-04)

Primary citation

Jakobsson, M.E.,Malecki, J.M.,Halabelian, L.,Nilges, B.S.,Pinto, R.,Kudithipudi, S.,Munk, S.,Davydova, E.,Zuhairi, F.R.,Arrowsmith, C.H.,Jeltsch, A.,Leidel, S.A.,Olsen, J.V.,Falnes, P.O.
The dual methyltransferase METTL13 targets N terminus and Lys55 of eEF1A and modulates codon-specific translation rates.
Nat Commun, 9:3411-3411, 2018

PubMed Abstract: Eukaryotic elongation factor 1 alpha (eEF1A) delivers aminoacyl-tRNA to the ribosome and thereby plays a key role in protein synthesis. Human eEF1A is subject to extensive post-translational methylation, but several of the responsible enzymes remain unknown. Using a wide range of experimental approaches, we here show that human methyltransferase (MTase)-like protein 13 (METTL13) contains two distinct MTase domains targeting the N terminus and Lys55 of eEF1A, respectively. Our biochemical and structural analyses provide detailed mechanistic insights into recognition of the eEF1A N terminus by METTL13. Moreover, through ribosome profiling, we demonstrate that loss of METTL13 function alters translation dynamics and results in changed translation rates of specific codons. In summary, we here unravel the function of a human MTase, showing that it methylates eEF1A and modulates mRNA translation in a codon-specific manner.

PubMed: 30143613
DOI: 10.1038/s41467-018-05646-y

Experimental method

X-RAY DIFFRACTION (1.7 Å)