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.

5e8j

From Proteopedia

(Difference between revisions)

Jump to: navigation, search

Revision as of 06:09, 10 July 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 1: / Line 1: @@
 ==Crystal structure of mRNA cap guanine-N7 methyltransferase in complex with RAM==
-<StructureSection load='5e8j' size='340' side='right' caption='[[5e8j]], [[Resolution|resolution]] 2.35&Aring;' scene=''>
+<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 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>
@@ Line 26: / Line 26: @@
 </StructureSection>
 [[Category: Human]]
+[[Category: Large Structures]]
 [[Category: Cowling, V]]
 [[Category: Petit, P]]

5e8j

From Proteopedia

Revision as of 06:09, 10 July 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

Personal tools

Navigation

Search

Toolbox