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5e8j

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Revision as of 07:09, 21 February 2019

Crystal structure of mRNA cap guanine-N7 methyltransferase in complex with RAM

Structural highlights

5e8j is a 4 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
Related:	3bgv, 3epp
Gene:	RNMT, KIAA0398 (HUMAN), FAM103A1, C15orf18 (HUMAN)
Activity:	mRNA (guanine-N(7)-)-methyltransferase, with EC number 2.1.1.56
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[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.^[1] ^[2] ^[3] ^[4] [RAM_HUMAN] Required for efficient mRNA cap methylation. Regulates RNMT expression by a post-transcriptional stabilizing mechanism.^[5]

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.

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^[6]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Tsukamoto T, Shibagaki Y, Niikura Y, Mizumoto K. Cloning and characterization of three human cDNAs encoding mRNA (guanine-7-)-methyltransferase, an mRNA cap methylase. Biochem Biophys Res Commun. 1998 Oct 9;251(1):27-34. PMID:9790902 doi:http://dx.doi.org/S0006-291X(98)99402-5
↑ Pillutla RC, Yue Z, Maldonado E, Shatkin AJ. Recombinant human mRNA cap methyltransferase binds capping enzyme/RNA polymerase IIo complexes. J Biol Chem. 1998 Aug 21;273(34):21443-6. PMID:9705270
↑ Saha N, Schwer B, Shuman S. Characterization of human, Schizosaccharomyces pombe, and Candida albicans mRNA cap methyltransferases and complete replacement of the yeast capping apparatus by mammalian enzymes. J Biol Chem. 1999 Jun 4;274(23):16553-62. PMID:10347220
↑ Gonatopoulos-Pournatzis T, Dunn S, Bounds R, Cowling VH. RAM/Fam103a1 is required for mRNA cap methylation. Mol Cell. 2011 Nov 18;44(4):585-96. doi: 10.1016/j.molcel.2011.08.041. PMID:22099306 doi:http://dx.doi.org/10.1016/j.molcel.2011.08.041
↑ Gonatopoulos-Pournatzis T, Dunn S, Bounds R, Cowling VH. RAM/Fam103a1 is required for mRNA cap methylation. Mol Cell. 2011 Nov 18;44(4):585-96. doi: 10.1016/j.molcel.2011.08.041. PMID:22099306 doi:http://dx.doi.org/10.1016/j.molcel.2011.08.041
↑ Varshney D, Petit AP, Bueren-Calabuig JA, Jansen C, Fletcher DA, Peggie M, Weidlich S, Scullion P, Pisliakov AV, Cowling VH. Molecular basis of RNA guanine-7 methyltransferase (RNMT) activation by RAM. Nucleic Acids Res. 2016 Jul 15. pii: gkw637. PMID:27422871 doi:http://dx.doi.org/10.1093/nar/gkw637

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5e8j"

@@ Line 3: / Line 3: @@
 <StructureSection load='5e8j' size='340' side='right' caption='[[5e8j]], [[Resolution|resolution]] 2.35&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5e8j]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5E8J OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5E8J FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5e8j]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5E8J OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5E8J FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SAH:S-ADENOSYL-L-HOMOCYSTEINE'>SAH</scene></td></tr>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3bgv|3bgv]], [[3epp|3epp]]</td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">RNMT, KIAA0398 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), FAM103A1, C15orf18 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
 <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/mRNA_(guanine-N(7)-)-methyltransferase mRNA (guanine-N(7)-)-methyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.1.1.56 2.1.1.56] </span></td></tr>
 <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5e8j FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5e8j OCA], [http://pdbe.org/5e8j PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5e8j RCSB], [http://www.ebi.ac.uk/pdbsum/5e8j PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5e8j ProSAT]</span></td></tr>
@@ Line 24: / Line 25: @@
 __TOC__
 </StructureSection>
+[[Category: Human]]
 [[Category: Cowling, V]]
 [[Category: Petit, P]]

5e8j

From Proteopedia

Revision as of 07:09, 21 February 2019

Crystal structure of mRNA cap guanine-N7 methyltransferase in complex with RAM

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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