4s3n

From Proteopedia

(Difference between revisions)

Revision as of 13:58, 26 March 2015

Crystal structure of human OAS3 domain I in complex with dsRNA

Structural highlights

4s3n is a 3 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Related:	4ig8, 1px5
Activity:	2'-5' oligoadenylate synthase, with EC number 2.7.7.84
Resources:	FirstGlance, OCA, RCSB, PDBsum

Function

[OAS3_HUMAN] Interferon-induced, dsRNA-activated antiviral enzyme which plays a critical role in cellular innate antiviral response. In addition, it may also play a role in other cellular processes such as apoptosis, cell growth, differentiation and gene regulation. Synthesizes preferentially dimers of 2'-5'-oligoadenylates (2-5A) from ATP which then bind to the inactive monomeric form of ribonuclease L (RNase L) leading to its dimerization and subsequent activation. Activation of RNase L leads to degradation of cellular as well as viral RNA, resulting in the inhibition of protein synthesis, thus terminating viral replication. Can mediate the antiviral effect via the classical RNase L-dependent pathway or an alternative antiviral pathway independent of RNase L. Displays antiviral activity against Chikungunya virus (CHIKV), Dengue virus, Sindbis virus (SINV) and Semliki forest virus (SFV).^[1] ^[2] ^[3]

Publication Abstract from PubMed

The mammalian innate immune system uses several sensors of double-stranded RNA (dsRNA) to develop the interferon response. Among these sensors are dsRNA-activated oligoadenylate synthetases (OAS), which produce signaling 2',5'-linked RNA molecules (2-5A) that activate regulated RNA decay in mammalian tissues. Different receptors from the OAS family contain one, two, or three copies of the 2-5A synthetase domain, which in several instances evolved into pseudoenzymes. The structures of the pseudoenzymatic domains and their roles in sensing dsRNA are unknown. Here we present the crystal structure of the first catalytically inactive domain of human OAS3 (hOAS3.DI) in complex with a 19-bp dsRNA, determined at 2.0-A resolution. The conformation of hOAS3.DI is different from the apo- and the dsRNA-bound states of the catalytically active homolog, OAS1, reported previously. The unique conformation of hOAS3.DI disables 2-5A synthesis by placing the active site residues nonproductively, but favors the binding of dsRNA. Biochemical data show that hOAS3.DI is essential for activation of hOAS3 and serves as a dsRNA-binding module, whereas the C-terminal domain DIII carries out catalysis. The location of the dsRNA-binding domain (DI) and the catalytic domain (DIII) at the opposite protein termini makes hOAS3 selective for long dsRNA. This mechanism relies on the catalytic inactivity of domain DI, revealing a surprising role of pseudoenzyme evolution in dsRNA surveillance.

Structural mechanism of sensing long dsRNA via a noncatalytic domain in human oligoadenylate synthetase 3.,Donovan J, Whitney G, Rath S, Korennykh A Proc Natl Acad Sci U S A. 2015 Mar 16. pii: 201419409. PMID:25775560^[4]

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

References

↑ Brehin AC, Casademont I, Frenkiel MP, Julier C, Sakuntabhai A, Despres P. The large form of human 2',5'-Oligoadenylate Synthetase (OAS3) exerts antiviral effect against Chikungunya virus. Virology. 2009 Feb 5;384(1):216-22. doi: 10.1016/j.virol.2008.10.021. Epub 2008, Dec 3. PMID:19056102 doi:http://dx.doi.org/10.1016/j.virol.2008.10.021
↑ Lin RJ, Yu HP, Chang BL, Tang WC, Liao CL, Lin YL. Distinct antiviral roles for human 2',5'-oligoadenylate synthetase family members against dengue virus infection. J Immunol. 2009 Dec 15;183(12):8035-43. doi: 10.4049/jimmunol.0902728. Epub . PMID:19923450 doi:http://dx.doi.org/10.4049/jimmunol.0902728
↑ Rebouillat D, Hovnanian A, Marie I, Hovanessian AG. The 100-kDa 2',5'-oligoadenylate synthetase catalyzing preferentially the synthesis of dimeric pppA2'p5'A molecules is composed of three homologous domains. J Biol Chem. 1999 Jan 15;274(3):1557-65. PMID:9880533
↑ Donovan J, Whitney G, Rath S, Korennykh A. Structural mechanism of sensing long dsRNA via a noncatalytic domain in human oligoadenylate synthetase 3. Proc Natl Acad Sci U S A. 2015 Mar 16. pii: 201419409. PMID:25775560 doi:http://dx.doi.org/10.1073/pnas.1419409112

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/4s3n"

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
+==Crystal structure of human OAS3 domain I in complex with dsRNA==
+<StructureSection load='4s3n' size='340' side='right' caption='[[4s3n]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[4s3n]] is a 3 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4S3N OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4S3N FirstGlance]. <br>
+</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4ig8|4ig8]], [[1px5|1px5]]</td></tr>
+<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/2'-5'_oligoadenylate_synthase 2'-5' oligoadenylate synthase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.7.84 2.7.7.84] </span></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=4s3n FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4s3n OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4s3n RCSB], [http://www.ebi.ac.uk/pdbsum/4s3n PDBsum]</span></td></tr>
+</table>
+== Function ==
+[[http://www.uniprot.org/uniprot/OAS3_HUMAN OAS3_HUMAN]] Interferon-induced, dsRNA-activated antiviral enzyme which plays a critical role in cellular innate antiviral response. In addition, it may also play a role in other cellular processes such as apoptosis, cell growth, differentiation and gene regulation. Synthesizes preferentially dimers of 2'-5'-oligoadenylates (2-5A) from ATP which then bind to the inactive monomeric form of ribonuclease L (RNase L) leading to its dimerization and subsequent activation. Activation of RNase L leads to degradation of cellular as well as viral RNA, resulting in the inhibition of protein synthesis, thus terminating viral replication. Can mediate the antiviral effect via the classical RNase L-dependent pathway or an alternative antiviral pathway independent of RNase L. Displays antiviral activity against Chikungunya virus (CHIKV), Dengue virus, Sindbis virus (SINV) and Semliki forest virus (SFV).<ref>PMID:19056102</ref> <ref>PMID:19923450</ref> <ref>PMID:9880533</ref>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+The mammalian innate immune system uses several sensors of double-stranded RNA (dsRNA) to develop the interferon response. Among these sensors are dsRNA-activated oligoadenylate synthetases (OAS), which produce signaling 2',5'-linked RNA molecules (2-5A) that activate regulated RNA decay in mammalian tissues. Different receptors from the OAS family contain one, two, or three copies of the 2-5A synthetase domain, which in several instances evolved into pseudoenzymes. The structures of the pseudoenzymatic domains and their roles in sensing dsRNA are unknown. Here we present the crystal structure of the first catalytically inactive domain of human OAS3 (hOAS3.DI) in complex with a 19-bp dsRNA, determined at 2.0-A resolution. The conformation of hOAS3.DI is different from the apo- and the dsRNA-bound states of the catalytically active homolog, OAS1, reported previously. The unique conformation of hOAS3.DI disables 2-5A synthesis by placing the active site residues nonproductively, but favors the binding of dsRNA. Biochemical data show that hOAS3.DI is essential for activation of hOAS3 and serves as a dsRNA-binding module, whereas the C-terminal domain DIII carries out catalysis. The location of the dsRNA-binding domain (DI) and the catalytic domain (DIII) at the opposite protein termini makes hOAS3 selective for long dsRNA. This mechanism relies on the catalytic inactivity of domain DI, revealing a surprising role of pseudoenzyme evolution in dsRNA surveillance.
-The entry 4s3n is ON HOLD
+Structural mechanism of sensing long dsRNA via a noncatalytic domain in human oligoadenylate synthetase 3.,Donovan J, Whitney G, Rath S, Korennykh A Proc Natl Acad Sci U S A. 2015 Mar 16. pii: 201419409. PMID:25775560<ref>PMID:25775560</ref>
-Authors: Donovan, J., Whitney, G., Rath, S., Korennykh, A.
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
-Description: Crystal structure of human OAS3 domain I in complex with dsRNA
+== References ==
-[[Category: Unreleased Structures]]
+<references/>
+__TOC__
+</StructureSection>
+[[Category: 2'-5' oligoadenylate synthase]]
+[[Category: Donovan, J]]
 [[Category: Korennykh, A]]
-[[Category: Donovan, J]]
+[[Category: Rath, S]]
 [[Category: Whitney, G]]
-[[Category: Rath, S]]
+[[Category: 2-5a]]
+[[Category: Dsrna]]
+[[Category: Oa]]
+[[Category: Oas1]]
+[[Category: Oas2]]
+[[Category: Oas3]]
+[[Category: Oasl]]
+[[Category: Rnase l]]
+[[Category: Transferase]]
+[[Category: Transferase-rna complex]]

4s3n

From Proteopedia

Revision as of 13:58, 26 March 2015

Crystal structure of human OAS3 domain I in complex with dsRNA

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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