This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.
Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.
8d58
From Proteopedia
(Difference between revisions)
| (One intermediate revision not shown.) | |||
| Line 1: | Line 1: | ||
| - | '''Unreleased structure''' | ||
| - | + | ==Crystal structure of human METTL1-WDR4 complex== | |
| + | <StructureSection load='8d58' size='340' side='right'caption='[[8d58]], [[Resolution|resolution]] 2.47Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[8d58]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8D58 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8D58 FirstGlance]. <br> | ||
| + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.47Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=IPA:ISOPROPYL+ALCOHOL'>IPA</scene></td></tr> | ||
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=8d58 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8d58 OCA], [https://pdbe.org/8d58 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8d58 RCSB], [https://www.ebi.ac.uk/pdbsum/8d58 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8d58 ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/TRMB_HUMAN TRMB_HUMAN] Catalyzes the formation of N(7)-methylguanine at position 46 (m7G46) in tRNA.<ref>PMID:12403464</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Specific, regulated modification of RNAs is important for proper gene expression(1,2). tRNAs are rich with various chemical modifications that affect their stability and function(3,4). 7-Methylguanosine (m(7)G) at tRNA position 46 is a conserved modification that modulates steady-state tRNA levels to affect cell growth(5,6). The METTL1-WDR4 complex generates m(7)G46 in humans, and dysregulation of METTL1-WDR4 has been linked to brain malformation and multiple cancers(7-22). 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 m(7)G 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 m(7)G modification by METTL1, providing the framework to understand its contribution to biology and disease. | ||
| - | + | Structures and mechanisms of tRNA methylation by METTL1-WDR4.,Ruiz-Arroyo VM, Raj R, Babu K, Onolbaatar O, Roberts PH, Nam Y Nature. 2023 Jan 4. doi: 10.1038/s41586-022-05565-5. PMID:36599982<ref>PMID:36599982</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| + | <div class="pdbe-citations 8d58" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Babu K]] | ||
| + | [[Category: Nam Y]] | ||
| + | [[Category: Raj R]] | ||
Current revision
Crystal structure of human METTL1-WDR4 complex
| |||||||||||
Categories: Homo sapiens | Large Structures | Babu K | Nam Y | Raj R
