6dcb: Difference between revisions

Latest revision as of 06:02, 11 October 2023

Structure of methylphosphate capping enzyme methyltransferase domain in complex with 5' end of 7SK RNA

Structural highlights

6dcb is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.998Å
Ligands:	GTP, SAH, SO4
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

MEPCE_HUMAN S-adenosyl-L-methionine-dependent methyltransferase that adds a methylphosphate cap at the 5'-end of 7SK snRNA, leading to stabilize it.^[1]

Publication Abstract from PubMed

Among RNA 5'-cap structures, gamma-phosphate monomethylation is unique to a small subset of noncoding RNAs, 7SK and U6 in humans. 7SK is capped by methylphosphate capping enzyme (MePCE), which has a second nonenzymatic role as a core component of the 7SK ribonuclear protein (RNP), an essential regulator of RNA transcription. We report 2.0- and 2.1-A X-ray crystal structures of the human MePCE methyltransferase domain bound to S-adenosylhomocysteine (SAH) and uncapped or capped 7SK substrates, respectively. 7SK recognition is achieved by protein contacts to a 5'-hairpin-single-stranded RNA region, thus explaining MePCE's specificity for 7SK and U6. The structures reveal SAH and product RNA in a near-transition-state geometry. Unexpectedly, binding experiments showed that MePCE has higher affinity for capped versus uncapped 7SK, and kinetic data support a model of slow product release. This work reveals the molecular mechanism of methyl transfer and 7SK retention by MePCE for subsequent assembly of 7SK RNP.

Structural basis of 7SK RNA 5'-gamma-phosphate methylation and retention by MePCE.,Yang Y, Eichhorn CD, Wang Y, Cascio D, Feigon J Nat Chem Biol. 2018 Dec 17. pii: 10.1038/s41589-018-0188-z. doi:, 10.1038/s41589-018-0188-z. PMID:30559425^[2]

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

References

↑ Jeronimo C, Forget D, Bouchard A, Li Q, Chua G, Poitras C, Therien C, Bergeron D, Bourassa S, Greenblatt J, Chabot B, Poirier GG, Hughes TR, Blanchette M, Price DH, Coulombe B. Systematic analysis of the protein interaction network for the human transcription machinery reveals the identity of the 7SK capping enzyme. Mol Cell. 2007 Jul 20;27(2):262-74. PMID:17643375 doi:https://dx.doi.org/10.1016/j.molcel.2007.06.027
↑ Yang Y, Eichhorn CD, Wang Y, Cascio D, Feigon J. Structural basis of 7SK RNA 5'-gamma-phosphate methylation and retention by MePCE. Nat Chem Biol. 2018 Dec 17. pii: 10.1038/s41589-018-0188-z. doi:, 10.1038/s41589-018-0188-z. PMID:30559425 doi:https://dx.doi.org/10.1038/s41589-018-0188-z

Proteopedia Page Contributors and Editors (what is this?)

OCA

[1] Jeronimo C, Forget D, Bouchard A, Li Q, Chua G, Poitras C, Therien C, Bergeron D, Bourassa S, Greenblatt J, Chabot B, Poirier GG, Hughes TR, Blanchette M, Price DH, Coulombe B. Systematic analysis of the protein interaction network for the human transcription machinery reveals the identity of the 7SK capping enzyme. Mol Cell. 2007 Jul 20;27(2):262-74. PMID:17643375 doi:https://dx.doi.org/10.1016/j.molcel.2007.06.027

[2] Yang Y, Eichhorn CD, Wang Y, Cascio D, Feigon J. Structural basis of 7SK RNA 5'-gamma-phosphate methylation and retention by MePCE. Nat Chem Biol. 2018 Dec 17. pii: 10.1038/s41589-018-0188-z. doi:, 10.1038/s41589-018-0188-z. PMID:30559425 doi:https://dx.doi.org/10.1038/s41589-018-0188-z

[1]

[2]

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 6dcb is ON HOLD
+==Structure of methylphosphate capping enzyme methyltransferase domain in complex with 5' end of 7SK RNA==
+<StructureSection load='6dcb' size='340' side='right'caption='[[6dcb]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[6dcb]] 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=6DCB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6DCB 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]] 1.998&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GTP:GUANOSINE-5-TRIPHOSPHATE'>GTP</scene>, <scene name='pdbligand=SAH:S-ADENOSYL-L-HOMOCYSTEINE'>SAH</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=6dcb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6dcb OCA], [https://pdbe.org/6dcb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6dcb RCSB], [https://www.ebi.ac.uk/pdbsum/6dcb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6dcb ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/MEPCE_HUMAN MEPCE_HUMAN] S-adenosyl-L-methionine-dependent methyltransferase that adds a methylphosphate cap at the 5'-end of 7SK snRNA, leading to stabilize it.<ref>PMID:17643375</ref>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Among RNA 5'-cap structures, gamma-phosphate monomethylation is unique to a small subset of noncoding RNAs, 7SK and U6 in humans. 7SK is capped by methylphosphate capping enzyme (MePCE), which has a second nonenzymatic role as a core component of the 7SK ribonuclear protein (RNP), an essential regulator of RNA transcription. We report 2.0- and 2.1-A X-ray crystal structures of the human MePCE methyltransferase domain bound to S-adenosylhomocysteine (SAH) and uncapped or capped 7SK substrates, respectively. 7SK recognition is achieved by protein contacts to a 5'-hairpin-single-stranded RNA region, thus explaining MePCE's specificity for 7SK and U6. The structures reveal SAH and product RNA in a near-transition-state geometry. Unexpectedly, binding experiments showed that MePCE has higher affinity for capped versus uncapped 7SK, and kinetic data support a model of slow product release. This work reveals the molecular mechanism of methyl transfer and 7SK retention by MePCE for subsequent assembly of 7SK RNP.
-Authors:
+Structural basis of 7SK RNA 5'-gamma-phosphate methylation and retention by MePCE.,Yang Y, Eichhorn CD, Wang Y, Cascio D, Feigon J Nat Chem Biol. 2018 Dec 17. pii: 10.1038/s41589-018-0188-z. doi:, 10.1038/s41589-018-0188-z. PMID:30559425<ref>PMID:30559425</ref>
-Description:
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
+<div class="pdbe-citations 6dcb" style="background-color:#fffaf0;"></div>
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Homo sapiens]]
+[[Category: Large Structures]]
+[[Category: Cascio D]]
+[[Category: Eichhorn C]]
+[[Category: Feigon J]]
+[[Category: Yang Y]]

6dcb: Difference between revisions

Latest revision as of 06:02, 11 October 2023

Structure of methylphosphate capping enzyme methyltransferase domain in complex with 5' end of 7SK RNA

Structural highlights

Function

Publication Abstract from PubMed

References

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