Database of articles cited by EMDB/PDB/SASBDB data

Keywords
Structure methods	All X-ray diffraction NMR electron microscopy small angle scattering neutron diffraction fiber diffraction powder diffraction infrared spectroscopy EPR fluorescence transfer theoretical model Hybrid
Author
Journal
IF	>30 >20 >10 >5 all

Title	Structures and mechanisms of tRNA methylation by METTL1-WDR4.
Journal, issue, pages	Nature, Vol. 613, Issue 7943, Page 383-390, Year 2023
Publish date	Jan 4, 2023
Authors	Victor M Ruiz-Arroyo / Rishi Raj / Kesavan Babu / Otgonbileg Onolbaatar / Paul H Roberts / Yunsun Nam /
PubMed Abstract	Specific, regulated modification of RNAs is important for proper gene expression. tRNAs are rich with various chemical modifications that affect their stability and function. 7-Methylguanosine (mG) ...Specific, regulated modification of RNAs is important for proper gene expression. tRNAs are rich with various chemical modifications that affect their stability and function. 7-Methylguanosine (mG) at tRNA position 46 is a conserved modification that modulates steady-state tRNA levels to affect cell growth. The METTL1-WDR4 complex generates mG46 in humans, and dysregulation of METTL1-WDR4 has been linked to brain malformation and multiple cancers. Here we show how METTL1 and WDR4 cooperate to recognize RNA substrates and catalyse methylation. A crystal structure of METTL1-WDR4 and cryo-electron microscopy structures of METTL1-WDR4-tRNA show that the composite protein surface recognizes the tRNA elbow through shape complementarity. The cryo-electron microscopy structures of METTL1-WDR4-tRNA with S-adenosylmethionine or S-adenosylhomocysteine along with METTL1 crystal structures provide additional insights into the catalytic mechanism by revealing the active site in multiple states. The METTL1 N terminus couples cofactor binding with conformational changes in the tRNA, the catalytic loop and the WDR4 C terminus, acting as the switch to activate mG methylation. Thus, our structural models explain how post-translational modifications of the METTL1 N terminus can regulate methylation. Together, our work elucidates the core and regulatory mechanisms underlying mG modification by METTL1, providing the framework to understand its contribution to biology and disease.
External links	Nature / PubMed:36599982 / PubMed Central
Methods	EM (single particle) / X-ray diffraction
Resolution	1.93 - 4.04 Å
Structure data	27264 8d9k EMDB-27264, PDB-8d9k: CryoEM structure of human METTL1-WDR4 in complex with Lys-tRNA Method: EM (single particle) / Resolution: 3.72 Å 27265 8d9l EMDB-27265, PDB-8d9l: CryoEM structure of human METTL1-WDR4 in complex with Lys-tRNA and SAM Method: EM (single particle) / Resolution: 4.04 Å 28108 8eg0 EMDB-28108, PDB-8eg0: CryoEM structure of human METTL1-WDR4 in complex with Lys-tRNA and SAH Method: EM (single particle) / Resolution: 3.53 Å PDB-8d58: Crystal structure of human METTL1-WDR4 complex Method: X-RAY DIFFRACTION / Resolution: 2.47 Å PDB-8d59: Crystal structure of human METTL1 in complex with SAM Method: X-RAY DIFFRACTION / Resolution: 2.26 Å PDB-8d5b: Crystal structure of human METTL1 in complex with SAH Method: X-RAY DIFFRACTION / Resolution: 1.93 Å
Chemicals	ChemComp-CL: Unknown entry / Chloride ChemComp-IPA: ISOPROPYL ALCOHOL / alkaloidYM / Isopropyl alcohol ChemComp-GOL: GLYCEROL / Glycerol ChemComp-HOH: WATER / Water ChemComp-SAM: S-ADENOSYLMETHIONINE / S-Adenosyl methionine ChemComp-SO4: SULFATE ION / Sulfate ChemComp-CAC: CACODYLATE ION / Cacodylic acid ChemComp-SAH*: S-ADENOSYL-L-HOMOCYSTEINE / S-Adenosyl-L-homocysteine
Source	homo sapiens (human)
Keywords	TRANSFERASE / Cancer protein / Methyl transferase / TRANSFERASE/RNA / TRANSFERASE-RNA complex