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6irw

From Proteopedia

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Current revision

Crystal structure of the human cap-specific adenosine methyltransferase bound to SAH

Structural highlights

6irw 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 2.9Å
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

CAPAM_HUMAN Cap-specific adenosine methyltransferase that catalyzes formation of N(6),2'-O-dimethyladenosine cap (m6A(m)) by methylating the adenosine at the second transcribed position of capped mRNAs (PubMed:30467178, PubMed:30487554, PubMed:31279658, PubMed:31279659, PubMed:33428944). Recruited to the early elongation complex of RNA polymerase II (RNAPII) via interaction with POLR2A and mediates formation of m6A(m) co-transcriptionally (PubMed:30467178).^[1] ^[2] ^[3] ^[4] ^[5]

Publication Abstract from PubMed

N (6)-methyladenosine (m(6)A), a major modification of mRNAs, plays critical roles in RNA metabolism and function. In addition to the internal m(6)A, N (6), 2'-O-dimethyladenosine (m(6)Am) is present at the transcription start nucleotide of capped mRNAs in vertebrates. However, its biogenesis and functional role remain elusive. Using a reverse genetics approach, we identified PCIF1, a factor that interacts with the Ser5-phosphorylated C-terminal domain of RNA polymerase II, as cap-specific adenosine methyltransferase (CAPAM) responsible for N (6)-methylation of m(6)Am. Crystal structure of CAPAM in complex with substrates revealed the molecular basis of cap-specific m(6)A formation. A transcriptome-wide analysis revealed that N (6)-methylation of m(6)Am promotes the translation of capped mRNAs. Thus, a cap-specific m(6)A writer promotes translation of mRNAs starting from m(6)Am.

Cap-specific terminal N (6)-methylation of RNA by an RNA polymerase II-associated methyltransferase.,Akichika S, Hirano S, Shichino Y, Suzuki T, Nishimasu H, Ishitani R, Sugita A, Hirose Y, Iwasaki S, Nureki O, Suzuki T Science. 2018 Nov 22. pii: science.aav0080. doi: 10.1126/science.aav0080. PMID:30467178^[6]

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

References

↑ Akichika S, Hirano S, Shichino Y, Suzuki T, Nishimasu H, Ishitani R, Sugita A, Hirose Y, Iwasaki S, Nureki O, Suzuki T. Cap-specific terminal N (6)-methylation of RNA by an RNA polymerase II-associated methyltransferase. Science. 2018 Nov 22. pii: science.aav0080. doi: 10.1126/science.aav0080. PMID:30467178 doi:http://dx.doi.org/10.1126/science.aav0080
↑ Sun H, Zhang M, Li K, Bai D, Yi C. Cap-specific, terminal N(6)-methylation by a mammalian m(6)Am methyltransferase. Cell Res. 2019 Jan;29(1):80-82. PMID:30487554 doi:10.1038/s41422-018-0117-4
↑ Boulias K, Toczydłowska-Socha D, Hawley BR, Liberman N, Takashima K, Zaccara S, Guez T, Vasseur JJ, Debart F, Aravind L, Jaffrey SR, Greer EL. Identification of the m(6)Am Methyltransferase PCIF1 Reveals the Location and Functions of m(6)Am in the Transcriptome. Mol Cell. 2019 Aug 8;75(3):631-643.e8. PMID:31279658 doi:10.1016/j.molcel.2019.06.006
↑ Sendinc E, Valle-Garcia D, Dhall A, Chen H, Henriques T, Navarrete-Perea J, Sheng W, Gygi SP, Adelman K, Shi Y. PCIF1 Catalyzes m6Am mRNA Methylation to Regulate Gene Expression. Mol Cell. 2019 Aug 8;75(3):620-630.e9. PMID:31279659 doi:10.1016/j.molcel.2019.05.030
↑ Yu D, Kaur G, Blumenthal RM, Zhang X, Cheng X. Enzymatic characterization of three human RNA adenosine methyltransferases reveals diverse substrate affinities and reaction optima. J Biol Chem. 2021 Jan-Jun;296:100270. PMID:33428944 doi:10.1016/j.jbc.2021.100270
↑ Akichika S, Hirano S, Shichino Y, Suzuki T, Nishimasu H, Ishitani R, Sugita A, Hirose Y, Iwasaki S, Nureki O, Suzuki T. Cap-specific terminal N (6)-methylation of RNA by an RNA polymerase II-associated methyltransferase. Science. 2018 Nov 22. pii: science.aav0080. doi: 10.1126/science.aav0080. PMID:30467178 doi:http://dx.doi.org/10.1126/science.aav0080

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/6irw"

@@ Line 1: / Line 1: @@
 ==Crystal structure of the human cap-specific adenosine methyltransferase bound to SAH==
-<StructureSection load='6irw' size='340' side='right' caption='[[6irw]], [[Resolution|resolution]] 2.90&Aring;' scene=''>
+<StructureSection load='6irw' size='340' side='right'caption='[[6irw]], [[Resolution|resolution]] 2.90&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6irw]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6IRW OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6IRW FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6irw]] 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=6IRW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6IRW FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=SAH:S-ADENOSYL-L-HOMOCYSTEINE'>SAH</scene></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.9&#8491;</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=6irw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6irw OCA], [http://pdbe.org/6irw PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6irw RCSB], [http://www.ebi.ac.uk/pdbsum/6irw PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6irw ProSAT]</span></td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SAH:S-ADENOSYL-L-HOMOCYSTEINE'>SAH</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=6irw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6irw OCA], [https://pdbe.org/6irw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6irw RCSB], [https://www.ebi.ac.uk/pdbsum/6irw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6irw ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[http://www.uniprot.org/uniprot/PCIF1_HUMAN PCIF1_HUMAN]] May play a role in transcription elongation or in coupling transcription to pre-mRNA processing through its association with the phosphorylated C-terminal domain (CTD) of RNAPII largest subunit.
+[https://www.uniprot.org/uniprot/CAPAM_HUMAN CAPAM_HUMAN] Cap-specific adenosine methyltransferase that catalyzes formation of N(6),2'-O-dimethyladenosine cap (m6A(m)) by methylating the adenosine at the second transcribed position of capped mRNAs (PubMed:30467178, PubMed:30487554, PubMed:31279658, PubMed:31279659, PubMed:33428944). Recruited to the early elongation complex of RNA polymerase II (RNAPII) via interaction with POLR2A and mediates formation of m6A(m) co-transcriptionally (PubMed:30467178).<ref>PMID:30467178</ref> <ref>PMID:30487554</ref> <ref>PMID:31279658</ref> <ref>PMID:31279659</ref> <ref>PMID:33428944</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 22: / Line 23: @@
 __TOC__
 </StructureSection>
-[[Category: Hirano, S]]
+[[Category: Homo sapiens]]
-[[Category: Ishitani, R]]
+[[Category: Large Structures]]
-[[Category: Nishimasu, H]]
+[[Category: Hirano S]]
-[[Category: Nureki, O]]
+[[Category: Ishitani R]]
-[[Category: M6a]]
+[[Category: Nishimasu H]]
-[[Category: Methyltransferase]]
+[[Category: Nureki O]]
-[[Category: N6-methyladenosine]]
-[[Category: Rna methylation]]
-[[Category: Transferase]]

6irw

From Proteopedia

Current revision

Crystal structure of the human cap-specific adenosine methyltransferase bound to SAH

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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