5e9w
From Proteopedia
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== Function == | == Function == | ||
[[http://www.uniprot.org/uniprot/MCES_HUMAN MCES_HUMAN]] mRNA-capping methyltransferase that methylates the N7 position of the added guanosine to the 5'-cap structure of mRNAs. Binds RNA containing 5'-terminal GpppC.<ref>PMID:9790902</ref> <ref>PMID:9705270</ref> <ref>PMID:10347220</ref> <ref>PMID:22099306</ref> | [[http://www.uniprot.org/uniprot/MCES_HUMAN MCES_HUMAN]] mRNA-capping methyltransferase that methylates the N7 position of the added guanosine to the 5'-cap structure of mRNAs. Binds RNA containing 5'-terminal GpppC.<ref>PMID:9790902</ref> <ref>PMID:9705270</ref> <ref>PMID:10347220</ref> <ref>PMID:22099306</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Maturation and translation of mRNA in eukaryotes requires the addition of the 7-methylguanosine cap. In vertebrates, the cap methyltransferase, RNA guanine-7 methyltransferase (RNMT), has an activating subunit, RNMT-Activating Miniprotein (RAM). Here we report the first crystal structure of the human RNMT in complex with the activation domain of RAM. A relatively unstructured and negatively charged RAM binds to a positively charged surface groove on RNMT, distal to the active site. This results in stabilisation of a RNMT lobe structure which co-evolved with RAM and is required for RAM binding. Structure-guided mutagenesis and molecular dynamics simulations reveal that RAM stabilises the structure and positioning of the RNMT lobe and the adjacent alpha-helix hinge, resulting in optimal positioning of helix A which contacts substrates in the active site. Using biophysical and biochemical approaches, we observe that RAM increases the recruitment of the methyl donor, AdoMet (S-adenosyl methionine), to RNMT. Thus we report the mechanism by which RAM allosterically activates RNMT, allowing it to function as a molecular rheostat for mRNA cap methylation. | ||
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| + | Molecular basis of RNA guanine-7 methyltransferase (RNMT) activation by RAM.,Varshney D, Petit AP, Bueren-Calabuig JA, Jansen C, Fletcher DA, Peggie M, Weidlich S, Scullion P, Pisliakov AV, Cowling VH Nucleic Acids Res. 2016 Jul 15. pii: gkw637. PMID:27422871<ref>PMID:27422871</ref> | ||
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| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 5e9w" style="background-color:#fffaf0;"></div> | ||
== References == | == References == | ||
<references/> | <references/> | ||
Revision as of 20:35, 3 August 2016
Crystal structure of mRNA cap guanine-N7 methyltransferase obtained by limited proteolysis
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