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2gth

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Revision as of 11:20, 27 March 2020

crystal structure of the wildtype MHV coronavirus non-structural protein nsp15

Structural highlights

2gth is a 1 chain structure with sequence from Cvma5. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[R1AB_CVMA5] The replicase polyprotein of coronaviruses is a multifunctional protein: it contains the activities necessary for the transcription of negative stranded RNA, leader RNA, subgenomic mRNAs and progeny virion RNA as well as proteinases responsible for the cleavage of the polyprotein into functional products. The papain-like proteinase 1 (PL1-PRO) and papain-like proteinase 2 (PL2-PRO) are responsible for the cleavages located at the N-terminus of the replicase polyprotein. In addition, PLP2 possesses a deubiquitinating/deISGylating activity and processes both 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains from cellular substrates. Antagonizes innate immune induction of type I interferon by blocking the phosphorylation, dimerization and subsequent nuclear translocation of host IRF-3 (By similarity). The main proteinase 3CL-PRO is responsible for the majority of cleavages as it cleaves the C-terminus of replicase polyprotein at 11 sites. Recognizes substrates containing the core sequence [ILMVF]-Q-|-[SGACN]. Inhibited by the substrate-analog Cbz-Val-Asn-Ser-Thr-Leu-Gln-CMK. Also contains an ADP-ribose-1-phosphate (ADRP)-binding function (By similarity). The helicase which contains a zinc finger structure displays RNA and DNA duplex-unwinding activities with 5' to 3' polarity. ATPase activity is strongly stimulated by poly(U), poly(dT), poly(C), poly(dA), but not by poly(G) (By similarity). The exoribonuclease acts on both ssRNA and dsRNA in a 3' to 5' direction (By similarity). Nsp7-nsp8 hexadecamer may possibly confer processivity to the polymerase, maybe by binding to dsRNA or by producing primers utilized by the latter (By similarity). Nsp9 is a ssRNA-binding protein (By similarity). NendoU is a Mn(2+)-dependent, uridylate-specific enzyme, which leaves 2'-3'-cyclic phosphates 5' to the cleaved bond (By similarity).

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

The unique coronavirus transcription/replication machinery comprised of multiple virus-encoded nonstructural proteins (nsp) plays a vital role during initial and intermediate phases of the viral life cycle. The crystal structure of mouse hepatitis virus strain A59 (MHV-A59) nsp15 is reported at 2.15-A resolution. nsp15 is an XendoU endoribonuclease and is the first one from this family to have its structure unveiled. The MHV-A59 nsp15 monomer structure has a novel protein fold. Two nsp15 trimers form a back-to-back hexamer that is believed to be the functional unit. The structure reveals the catalytic site including the highly conserved residues His262, His277, and Lys317, which is supported by mutagenesis analysis. Gel filtration and enzyme activity assays confirmed that the hexamer is the active form for nsp15 and demonstrate the specificity of nsp15 for uridylate. The high sequence conservation of nsp15 in coronaviruses, including that of severe acute respiratory syndrome, suggests that this protein may provide a new target for the design of antiviral therapeutics.

New antiviral target revealed by the hexameric structure of mouse hepatitis virus nonstructural protein nsp15.,Xu X, Zhai Y, Sun F, Lou Z, Su D, Xu Y, Zhang R, Joachimiak A, Zhang XC, Bartlam M, Rao Z J Virol. 2006 Aug;80(16):7909-17. PMID:16873248^[1]

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

References

↑ Xu X, Zhai Y, Sun F, Lou Z, Su D, Xu Y, Zhang R, Joachimiak A, Zhang XC, Bartlam M, Rao Z. New antiviral target revealed by the hexameric structure of mouse hepatitis virus nonstructural protein nsp15. J Virol. 2006 Aug;80(16):7909-17. PMID:16873248 doi:80/16/7909

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2gth"

@@ Line 1: / Line 1: @@
 ==crystal structure of the wildtype MHV coronavirus non-structural protein nsp15==
-<StructureSection load='2gth' size='340' side='right' caption='[[2gth]], [[Resolution|resolution]] 2.70&Aring;' scene=''>
+<StructureSection load='2gth' size='340' side='right'caption='[[2gth]], [[Resolution|resolution]] 2.70&Aring;' scene=''>
 == Structural highlights ==
 <table><tr><td colspan='2'>[[2gth]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Cvma5 Cvma5]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2GTH OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2GTH FirstGlance]. <br>
@@ Line 32: / Line 32: @@
 </StructureSection>
 [[Category: Cvma5]]
+[[Category: Large Structures]]
 [[Category: Lou, Z]]
 [[Category: Rao, Z]]

2gth

From Proteopedia

Revision as of 11:20, 27 March 2020

crystal structure of the wildtype MHV coronavirus non-structural protein nsp15

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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