6dcc

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

spinqualitylabelsall models 6dcc, resolution 2.10Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6dcc is a 2 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: SAH, SO4 NonStd Res: G5J Gene: MEPCE, BCDIN3 (HUMAN) 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. 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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