5ed1

From Proteopedia

(Difference between revisions)

Current revision

Human Adenosine Deaminase Acting on dsRNA (ADAR2) mutant E488Q bound to dsRNA sequence derived from S. cerevisiae BDF2 gene

Structural highlights

5ed1 is a 4 chain structure with sequence from Homo sapiens and Saccharomyces cerevisiae. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.77Å
Ligands:	, ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

RED1_HUMAN Catalyzes the hydrolytic deamination of adenosine to inosine in double-stranded RNA (dsRNA) referred to as A-to-I RNA editing. This may affect gene expression and function in a number of ways that include mRNA translation by changing codons and hence the amino acid sequence of proteins; pre-mRNA splicing by altering splice site recognition sequences; RNA stability by changing sequences involved in nuclease recognition; genetic stability in the case of RNA virus genomes by changing sequences during viral RNA replication; and RNA structure-dependent activities such as microRNA production or targeting or protein-RNA interactions. Can edit both viral and cellular RNAs and can edit RNAs at multiple sites (hyper-editing) or at specific sites (site-specific editing). Its cellular RNA substrates include: bladder cancer-associated protein (BLCAP), neurotransmitter receptors for glutamate (GRIA2 and GRIK2) and serotonin (HTR2C), GABA receptor (GABRA3) and potassium voltage-gated channel (KCNA1). Site-specific RNA editing of transcripts encoding these proteins results in amino acid substitutions which consequently alter their functional activities. Edits GRIA2 at both the Q/R and R/G sites efficiently but converts the adenosine in hotspot1 much less efficiently. Can exert a proviral effect towards human immunodeficiency virus type 1 (HIV-1) and enhances its replication via both an editing-dependent and editing-independent mechanism. The former involves editing of adenosines in the 5'UTR while the latter occurs via suppression of EIF2AK2/PKR activation and function. Can inhibit cell proliferation and migration and can stimulate exocytosis.^[1] ^[2] ^[3]

Publication Abstract from PubMed

Adenosine deaminases acting on RNA (ADARs) are editing enzymes that convert adenosine to inosine in duplex RNA, a modification reaction with wide-ranging consequences in RNA function. Understanding of the ADAR reaction mechanism, the origin of editing-site selectivity, and the effect of mutations is limited by the lack of high-resolution structural data for complexes of ADARs bound to substrate RNAs. Here we describe four crystal structures of the human ADAR2 deaminase domain bound to RNA duplexes bearing a mimic of the deamination reaction intermediate. These structures, together with structure-guided mutagenesis and RNA-modification experiments, explain the basis of the ADAR deaminase domain's dsRNA specificity, its base-flipping mechanism, and its nearest-neighbor preferences. In addition, we identified an ADAR2-specific RNA-binding loop near the enzyme active site, thus rationalizing differences in selectivity observed between different ADARs. Finally, our results provide a structural framework for understanding the effects of ADAR mutations associated with human disease.

Structures of human ADAR2 bound to dsRNA reveal base-flipping mechanism and basis for site selectivity.,Matthews MM, Thomas JM, Zheng Y, Tran K, Phelps KJ, Scott AI, Havel J, Fisher AJ, Beal PA Nat Struct Mol Biol. 2016 May;23(5):426-33. doi: 10.1038/nsmb.3203. Epub 2016 Apr, 11. PMID:27065196^[4]

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

References

↑ Cenci C, Barzotti R, Galeano F, Corbelli S, Rota R, Massimi L, Di Rocco C, O'Connell MA, Gallo A. Down-regulation of RNA editing in pediatric astrocytomas: ADAR2 editing activity inhibits cell migration and proliferation. J Biol Chem. 2008 Mar 14;283(11):7251-60. doi: 10.1074/jbc.M708316200. Epub 2008 , Jan 4. PMID:18178553 doi:http://dx.doi.org/10.1074/jbc.M708316200
↑ Galeano F, Leroy A, Rossetti C, Gromova I, Gautier P, Keegan LP, Massimi L, Di Rocco C, O'Connell MA, Gallo A. Human BLCAP transcript: new editing events in normal and cancerous tissues. Int J Cancer. 2010 Jul 1;127(1):127-37. doi: 10.1002/ijc.25022. PMID:19908260 doi:10.1002/ijc.25022
↑ Doria M, Tomaselli S, Neri F, Ciafre SA, Farace MG, Michienzi A, Gallo A. ADAR2 editing enzyme is a novel human immunodeficiency virus-1 proviral factor. J Gen Virol. 2011 May;92(Pt 5):1228-32. doi: 10.1099/vir.0.028043-0. Epub 2011, Feb 2. PMID:21289159 doi:10.1099/vir.0.028043-0
↑ Matthews MM, Thomas JM, Zheng Y, Tran K, Phelps KJ, Scott AI, Havel J, Fisher AJ, Beal PA. Structures of human ADAR2 bound to dsRNA reveal base-flipping mechanism and basis for site selectivity. Nat Struct Mol Biol. 2016 May;23(5):426-33. doi: 10.1038/nsmb.3203. Epub 2016 Apr, 11. PMID:27065196 doi:http://dx.doi.org/10.1038/nsmb.3203

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5ed1"

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 5ed1 is ON HOLD
+==Human Adenosine Deaminase Acting on dsRNA (ADAR2) mutant E488Q bound to dsRNA sequence derived from S. cerevisiae BDF2 gene==
+<StructureSection load='5ed1' size='340' side='right'caption='[[5ed1]], [[Resolution|resolution]] 2.77&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[5ed1]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Saccharomyces_cerevisiae Saccharomyces cerevisiae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5ED1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5ED1 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]] 2.77&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=8AZ:8-AZA-NEBULARINE-5-MONOPHOSPHATE'>8AZ</scene>, <scene name='pdbligand=IHP:INOSITOL+HEXAKISPHOSPHATE'>IHP</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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=5ed1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ed1 OCA], [https://pdbe.org/5ed1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5ed1 RCSB], [https://www.ebi.ac.uk/pdbsum/5ed1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5ed1 ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/RED1_HUMAN RED1_HUMAN] Catalyzes the hydrolytic deamination of adenosine to inosine in double-stranded RNA (dsRNA) referred to as A-to-I RNA editing. This may affect gene expression and function in a number of ways that include mRNA translation by changing codons and hence the amino acid sequence of proteins; pre-mRNA splicing by altering splice site recognition sequences; RNA stability by changing sequences involved in nuclease recognition; genetic stability in the case of RNA virus genomes by changing sequences during viral RNA replication; and RNA structure-dependent activities such as microRNA production or targeting or protein-RNA interactions. Can edit both viral and cellular RNAs and can edit RNAs at multiple sites (hyper-editing) or at specific sites (site-specific editing). Its cellular RNA substrates include: bladder cancer-associated protein (BLCAP), neurotransmitter receptors for glutamate (GRIA2 and GRIK2) and serotonin (HTR2C), GABA receptor (GABRA3) and potassium voltage-gated channel (KCNA1). Site-specific RNA editing of transcripts encoding these proteins results in amino acid substitutions which consequently alter their functional activities. Edits GRIA2 at both the Q/R and R/G sites efficiently but converts the adenosine in hotspot1 much less efficiently. Can exert a proviral effect towards human immunodeficiency virus type 1 (HIV-1) and enhances its replication via both an editing-dependent and editing-independent mechanism. The former involves editing of adenosines in the 5'UTR while the latter occurs via suppression of EIF2AK2/PKR activation and function. Can inhibit cell proliferation and migration and can stimulate exocytosis.<ref>PMID:18178553</ref> <ref>PMID:19908260</ref> <ref>PMID:21289159</ref>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Adenosine deaminases acting on RNA (ADARs) are editing enzymes that convert adenosine to inosine in duplex RNA, a modification reaction with wide-ranging consequences in RNA function. Understanding of the ADAR reaction mechanism, the origin of editing-site selectivity, and the effect of mutations is limited by the lack of high-resolution structural data for complexes of ADARs bound to substrate RNAs. Here we describe four crystal structures of the human ADAR2 deaminase domain bound to RNA duplexes bearing a mimic of the deamination reaction intermediate. These structures, together with structure-guided mutagenesis and RNA-modification experiments, explain the basis of the ADAR deaminase domain's dsRNA specificity, its base-flipping mechanism, and its nearest-neighbor preferences. In addition, we identified an ADAR2-specific RNA-binding loop near the enzyme active site, thus rationalizing differences in selectivity observed between different ADARs. Finally, our results provide a structural framework for understanding the effects of ADAR mutations associated with human disease.
-Authors: Matthews, M.M., Fisher, A.J., Beal, P.A.
+Structures of human ADAR2 bound to dsRNA reveal base-flipping mechanism and basis for site selectivity.,Matthews MM, Thomas JM, Zheng Y, Tran K, Phelps KJ, Scott AI, Havel J, Fisher AJ, Beal PA Nat Struct Mol Biol. 2016 May;23(5):426-33. doi: 10.1038/nsmb.3203. Epub 2016 Apr, 11. PMID:27065196<ref>PMID:27065196</ref>
-Description: Human Adenosine Deaminase Acting on dsRNA (ADAR2) mutant E488Q bound to dsRNA sequence derived from S. cerevisiae BDF2 gene
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
-[[Category: Fisher, A.J]]
+<div class="pdbe-citations 5ed1" style="background-color:#fffaf0;"></div>
-[[Category: Matthews, M.M]]
-[[Category: Beal, P.A]]
+==See Also==
+*[[Adenosine deaminase 3D structures|Adenosine deaminase 3D structures]]
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Homo sapiens]]
+[[Category: Large Structures]]
+[[Category: Saccharomyces cerevisiae]]
+[[Category: Beal PA]]
+[[Category: Fisher AJ]]
+[[Category: Matthews MM]]

5ed1

From Proteopedia

Current revision

Human Adenosine Deaminase Acting on dsRNA (ADAR2) mutant E488Q bound to dsRNA sequence derived from S. cerevisiae BDF2 gene

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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