6tgz

From Proteopedia

(Difference between revisions)

Current revision

IE1 from human cytomegalovirus

Structural highlights

6tgz is a 1 chain structure with sequence from Human herpesvirus 5 strain AD169. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 3.2Å
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

VIE1_HCMVA Plays an important role in transactivating viral early genes as well as activating its own promoter, probably by altering the viral chromatin structure (By similarity). Expression of IE1 and IE2 proteins is critical for the establishment of lytic infection and reactivation from viral latency (PubMed:27466417). Disrupts PML-associated ND10 nuclear bodies by interfering with host PML and SP100 sumoylation thereby altering the regulation of type I and type II interferon-induced gene expression (Probable) (PubMed:27903803). Promotes efficient viral growth by interacting with and directing host SP100 to degradation, leading to enhanced acetylation level of histones (By similarity). In addition, functions in counteracting the host innate antiviral response. Inhibits the type I interferon pathway by directly interacting with and sequestrating host STAT2 (By similarity). Also targets type II interferon pathway by repressing IL6- and STAT3 target genes (By similarity). Repression of STAT3 genes is due to STAT3 nuclear accumulation and disruption of IL6-induced STAT3 phosphorylation by IE1 (PubMed:23903834). This repression is followed by phosphorylation and activation of STAT1 (By similarity). Inhibits host ISG transcription by sequestering host ISGF3 in a PML- and STAT2- binding dependent manner (By similarity). Alters host cell cycle progression, probably through its interaction with host E2F1 or RB1 that overcomes the RB1-mediated repression of E2F-responsive promoters (By similarity).[UniProtKB:P03169]^[1] ^[2] ^[3] ^[4]

Publication Abstract from PubMed

Restriction factors are potent antiviral proteins that constitute a first line of intracellular defense by blocking viral replication and spread. During co-evolution, however, viruses have developed antagonistic proteins to modulate or degrade the restriction factors of their host. To ensure the success of lytic replication, the herpesvirus human cytomegalovirus (HCMV) expresses the immediate-early protein IE1, which acts as an antagonist of antiviral, subnuclear structures termed PML nuclear bodies (PML-NBs). IE1 interacts directly with PML, the key protein of PML-NBs, through its core domain and disrupts the dot-like multiprotein complexes thereby abrogating the antiviral effects. Here we present the crystal structures of the human and rat cytomegalovirus core domain (IE1CORE). We found that IE1CORE domains, also including the previously characterized IE1CORE of rhesus CMV, form a distinct class of proteins that are characterized by a highly similar and unique tertiary fold and quaternary assembly. This contrasts to a marked amino acid sequence diversity suggesting that strong positive selection evolved a conserved fold, while immune selection pressure may have fostered sequence divergence of IE1. At the same time, we detected specific differences in the helix arrangements of primate versus rodent IE1CORE structures. Functional characterization revealed a conserved mechanism of PML-NB disruption, however, primate and rodent IE1 proteins were only effective in cells of the natural host species but not during cross-species infection. Remarkably, we observed that expression of HCMV IE1 allows rat cytomegalovirus replication in human cells. We conclude that cytomegaloviruses have evolved a distinct protein tertiary structure of IE1 to effectively bind and inactivate an important cellular restriction factor. Furthermore, our data show that the IE1 fold has been adapted to maximize the efficacy of PML targeting in a species-specific manner and support the concept that the PML-NBs-based intrinsic defense constitutes a barrier to cross-species transmission of HCMV.

Cytomegalovirus immediate-early 1 proteins form a structurally distinct protein class with adaptations determining cross-species barriers.,Schweininger J, Scherer M, Rothemund F, Schilling EM, Worz S, Stamminger T, Muller YA PLoS Pathog. 2021 Aug 9;17(8):e1009863. doi: 10.1371/journal.ppat.1009863., eCollection 2021 Aug. PMID:34370791^[5]

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

References

↑ Reitsma JM, Sato H, Nevels M, Terhune SS, Paulus C. Human cytomegalovirus IE1 protein disrupts interleukin-6 signaling by sequestering STAT3 in the nucleus. J Virol. 2013 Oct;87(19):10763-76. doi: 10.1128/JVI.01197-13. Epub 2013 Jul 31. PMID:23903834 doi:http://dx.doi.org/10.1128/JVI.01197-13
↑ Arend KC, Ziehr B, Vincent HA, Moorman NJ. Multiple Transcripts Encode Full-Length Human Cytomegalovirus IE1 and IE2 Proteins during Lytic Infection. J Virol. 2016 Sep 12;90(19):8855-65. doi: 10.1128/JVI.00741-16. Print 2016 Oct 1. PMID:27466417 doi:http://dx.doi.org/10.1128/JVI.00741-16
↑ Schilling EM, Scherer M, Reuter N, Schweininger J, Muller YA, Stamminger T. The Human Cytomegalovirus IE1 Protein Antagonizes PML Nuclear Body-Mediated Intrinsic Immunity via the Inhibition of PML De Novo SUMOylation. J Virol. 2017 Jan 31;91(4). pii: JVI.02049-16. doi: 10.1128/JVI.02049-16. Print, 2017 Feb 15. PMID:27903803 doi:http://dx.doi.org/10.1128/JVI.02049-16
↑ Scherer M, Otto V, Stump JD, Klingl S, Muller R, Reuter N, Muller YA, Sticht H, Stamminger T. Characterization of Recombinant Human Cytomegaloviruses Encoding IE1 Mutants L174P and 1-382 Reveals that Viral Targeting of PML Bodies Perturbs both Intrinsic and Innate Immune Responses. J Virol. 2015 Nov 11;90(3):1190-205. doi: 10.1128/JVI.01973-15. Print 2016 Feb 1. PMID:26559840 doi:http://dx.doi.org/10.1128/JVI.01973-15
↑ Schweininger J, Scherer M, Rothemund F, Schilling EM, Worz S, Stamminger T, Muller YA. Cytomegalovirus immediate-early 1 proteins form a structurally distinct protein class with adaptations determining cross-species barriers. PLoS Pathog. 2021 Aug 9;17(8):e1009863. doi: 10.1371/journal.ppat.1009863., eCollection 2021 Aug. PMID:34370791 doi:http://dx.doi.org/10.1371/journal.ppat.1009863

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/6tgz"

Categories: Human herpesvirus 5 strain AD169 | Large Structures | Muller YA | Schweininger J

@@ Line 3: / Line 3: @@
 <StructureSection load='6tgz' size='340' side='right'caption='[[6tgz]], [[Resolution|resolution]] 3.20&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6tgz]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Hcmva Hcmva]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6TGZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6TGZ FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6tgz]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Human_herpesvirus_5_strain_AD169 Human herpesvirus 5 strain AD169]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6TGZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6TGZ FirstGlance]. <br>
-</td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">UL123 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10360 HCMVA])</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]] 3.2&#8491;</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=6tgz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6tgz OCA], [https://pdbe.org/6tgz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6tgz RCSB], [https://www.ebi.ac.uk/pdbsum/6tgz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6tgz ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[https://www.uniprot.org/uniprot/VIE1_HCMVA VIE1_HCMVA]] Plays an important role in transactivating viral early genes as well as activating its own promoter, probably by altering the viral chromatin structure (By similarity). Expression of IE1 and IE2 proteins is critical for the establishment of lytic infection and reactivation from viral latency (PubMed:27466417). Disrupts PML-associated ND10 nuclear bodies by interfering with host PML and SP100 sumoylation thereby altering the regulation of type I and type II interferon-induced gene expression (Probable) (PubMed:27903803). Promotes efficient viral growth by interacting with and directing host SP100 to degradation, leading to enhanced acetylation level of histones (By similarity). In addition, functions in counteracting the host innate antiviral response. Inhibits the type I interferon pathway by directly interacting with and sequestrating host STAT2 (By similarity). Also targets type II interferon pathway by repressing IL6- and STAT3 target genes (By similarity). Repression of STAT3 genes is due to STAT3 nuclear accumulation and disruption of IL6-induced STAT3 phosphorylation by IE1 (PubMed:23903834). This repression is followed by phosphorylation and activation of STAT1 (By similarity). Inhibits host ISG transcription by sequestering host ISGF3 in a PML- and STAT2- binding dependent manner (By similarity). Alters host cell cycle progression, probably through its interaction with host E2F1 or RB1 that overcomes the RB1-mediated repression of E2F-responsive promoters (By similarity).[UniProtKB:P03169]<ref>PMID:23903834</ref> <ref>PMID:27466417</ref> <ref>PMID:27903803</ref> <ref>PMID:26559840</ref>
+[https://www.uniprot.org/uniprot/VIE1_HCMVA VIE1_HCMVA] Plays an important role in transactivating viral early genes as well as activating its own promoter, probably by altering the viral chromatin structure (By similarity). Expression of IE1 and IE2 proteins is critical for the establishment of lytic infection and reactivation from viral latency (PubMed:27466417). Disrupts PML-associated ND10 nuclear bodies by interfering with host PML and SP100 sumoylation thereby altering the regulation of type I and type II interferon-induced gene expression (Probable) (PubMed:27903803). Promotes efficient viral growth by interacting with and directing host SP100 to degradation, leading to enhanced acetylation level of histones (By similarity). In addition, functions in counteracting the host innate antiviral response. Inhibits the type I interferon pathway by directly interacting with and sequestrating host STAT2 (By similarity). Also targets type II interferon pathway by repressing IL6- and STAT3 target genes (By similarity). Repression of STAT3 genes is due to STAT3 nuclear accumulation and disruption of IL6-induced STAT3 phosphorylation by IE1 (PubMed:23903834). This repression is followed by phosphorylation and activation of STAT1 (By similarity). Inhibits host ISG transcription by sequestering host ISGF3 in a PML- and STAT2- binding dependent manner (By similarity). Alters host cell cycle progression, probably through its interaction with host E2F1 or RB1 that overcomes the RB1-mediated repression of E2F-responsive promoters (By similarity).[UniProtKB:P03169]<ref>PMID:23903834</ref> <ref>PMID:27466417</ref> <ref>PMID:27903803</ref> <ref>PMID:26559840</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 22: / Line 22: @@
 __TOC__
 </StructureSection>
-[[Category: Hcmva]]
+[[Category: Human herpesvirus 5 strain AD169]]
 [[Category: Large Structures]]
-[[Category: Muller, Y A]]
+[[Category: Muller YA]]
-[[Category: Schweininger, J]]
+[[Category: Schweininger J]]
-[[Category: Hcmv ie1]]
-[[Category: Viral protein]]

6tgz

From Proteopedia

Current revision

IE1 from human cytomegalovirus

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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