|
|
| (One intermediate revision not shown.) |
| Line 1: |
Line 1: |
| | | | |
| | ==Solution structure of MHV nsp3a== | | ==Solution structure of MHV nsp3a== |
| - | <StructureSection load='2m0a' size='340' side='right'caption='[[2m0a]], [[NMR_Ensembles_of_Models | 21 NMR models]]' scene=''> | + | <StructureSection load='2m0a' size='340' side='right'caption='[[2m0a]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2m0a]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Cvma5 Cvma5]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2M0A OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2M0A FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2m0a]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Murine_hepatitis_virus_strain_A59 Murine hepatitis virus strain A59]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2M0A OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2M0A FirstGlance]. <br> |
| - | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">1a ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=11142 CVMA5])</td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</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=2m0a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2m0a OCA], [https://pdbe.org/2m0a PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2m0a RCSB], [https://www.ebi.ac.uk/pdbsum/2m0a PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2m0a ProSAT]</span></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=2m0a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2m0a OCA], [https://pdbe.org/2m0a PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2m0a RCSB], [https://www.ebi.ac.uk/pdbsum/2m0a PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2m0a ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/R1A_CVMA5 R1A_CVMA5]] 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). 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).
| + | [https://www.uniprot.org/uniprot/R1A_CVMA5 R1A_CVMA5] 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). 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). |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
| Line 22: |
Line 22: |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Cvma5]] | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Giedroc, D P]] | + | [[Category: Murine hepatitis virus strain A59]] |
| - | [[Category: Keane, S C]] | + | [[Category: Giedroc DP]] |
| - | [[Category: Hydrolase]] | + | [[Category: Keane SC]] |
| Structural highlights
Function
R1A_CVMA5 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). 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).
Publication Abstract from PubMed
Coronaviruses (CoVs) are positive-sense, single-stranded, enveloped RNA viruses that infect a variety of vertebrate hosts. The CoV nucleocapsid (N) protein contains two structurally independent RNA binding domains denoted the N-terminal domain (NTD) and the dimeric C-terminal (CTD) domain joined by a charged linker region rich in serine and arginine residues (SR-rich linker). An important goal in unraveling N function is to molecularly characterize N-protein interactions. Recent genetic evidence suggests that N interacts with nsp3a, a component of the viral replicase. Here, we present the solution NMR structure of MHV nsp3a and show, using isothermal titration calorimetry, that MHV N219, an N construct that extends into the SR-rich linker (residues 60-219), binds cognate nsp3a with high affinity (K(a) = 1.4 (+/-0.3) x 10(6) M(-1)). In contrast, neither N197, an N construct containing only the folded NTD (residues 60-197), or the CTD dimer (residues 260-380), bind nsp3a with detectable affinity. This indicates that the key nsp3a binding determinants localize to the SR-rich linker, a finding consistent with reverse genetics studies. NMR chemical shift perturbation analysis reveals that the N-terminal region of an MHV N SR-rich linker peptide (residues 198-230) binds to the acidic face of MHV nsp3a containing the acidic alpha2 helix with an affinity K(a) of 8.3 x 10(3) M(-1). These studies reveal that the SR-rich linker of MHV N is necessary but not sufficient to maintain this high-affinity binding to N.
Solution structure of mouse hepatitis virus (MHV) nsp3a and determinants of the interaction with MHV nucleocapsid (N) protein.,Keane SC, Giedroc DP J Virol. 2013 Jan 9. PMID:23302895[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Keane SC, Giedroc DP. Solution structure of mouse hepatitis virus (MHV) nsp3a and determinants of the interaction with MHV nucleocapsid (N) protein. J Virol. 2013 Jan 9. PMID:23302895 doi:http://dx.doi.org/10.1128/JVI.03112-12
|
