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| | ==Crystal structure of fragment 1600-1733 of HSV1 UL36, native== | | ==Crystal structure of fragment 1600-1733 of HSV1 UL36, native== |
| - | <StructureSection load='4tt1' size='340' side='right' caption='[[4tt1]], [[Resolution|resolution]] 2.75Å' scene=''> | + | <StructureSection load='4tt1' size='340' side='right'caption='[[4tt1]], [[Resolution|resolution]] 2.75Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4tt1]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4TT1 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4TT1 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4tt1]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Human_alphaherpesvirus_1_strain_17 Human alphaherpesvirus 1 strain 17]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4TT1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4TT1 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></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]] 2.75Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4tt0|4tt0]]</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></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=4tt1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4tt1 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4tt1 RCSB], [http://www.ebi.ac.uk/pdbsum/4tt1 PDBsum]</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=4tt1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4tt1 OCA], [https://pdbe.org/4tt1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4tt1 RCSB], [https://www.ebi.ac.uk/pdbsum/4tt1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4tt1 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/DEN_HHV11 DEN_HHV11]] Deneddylase that deregulates the host cell cycle S phase to create a favorable environment allowing efficient viral genome replication. Interacts with and deneddylates host cullins including CUL1 and CUL4A, thereby reducing their E3 ubiquitin ligase activity. Inhibition of cullins leads to the stabilization of cullin-RING ligase substrates such as host CDN1A/p21, CDKN1B/p27kip and CDC25A, preventing S phase progression. Additionally, acts as a deubiquitinase and cleaves both 'Lys-48' and 'Lys-63'-linked ubiquitin chains (By similarity). | + | [https://www.uniprot.org/uniprot/LTP_HHV11 LTP_HHV11] Large tegument protein that plays multiple roles in the viral cycle. During viral entry, remains associated with the capsid while most of the tegument is detached and participates in the capsid transport toward the host nucleus. Plays a role in the routing of the capsid at the nuclear pore complex and subsequent uncoating. Within the host nucleus, acts as a deneddylase and promotes the degradation of nuclear CRLs (cullin-RING ubiquitin ligases) and thereby stabilizes nuclear CRL substrates, while cytoplasmic CRLs remain unaffected. These modifications prevent host cell cycle S-phase progression and create a favorable environment allowing efficient viral genome replication. Participates later in the secondary envelopment of capsids. Indeed, plays a linker role for the association of the outer viral tegument to the capsids together with the inner tegument protein.[HAMAP-Rule:MF_04044]<ref>PMID:16306630</ref> <ref>PMID:18216103</ref> <ref>PMID:18495763</ref> <ref>PMID:18971278</ref> <ref>PMID:19923173</ref> <ref>PMID:20190741</ref> <ref>PMID:22345483</ref> <ref>PMID:22718835</ref> <ref>PMID:23186167</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| | </div> | | </div> |
| | + | <div class="pdbe-citations 4tt1" style="background-color:#fffaf0;"></div> |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Bressanelli, S]] | + | [[Category: Human alphaherpesvirus 1 strain 17]] |
| - | [[Category: Roche, S]] | + | [[Category: Large Structures]] |
| - | [[Category: Scrima, N]] | + | [[Category: Bressanelli S]] |
| - | [[Category: Fibrous protein]] | + | [[Category: Roche S]] |
| - | [[Category: Hydrolase]] | + | [[Category: Scrima N]] |
| - | [[Category: Protein fibril]]
| + | |
| - | [[Category: Tegument protein]]
| + | |
| - | [[Category: Viral protein]]
| + | |
| Structural highlights
Function
LTP_HHV11 Large tegument protein that plays multiple roles in the viral cycle. During viral entry, remains associated with the capsid while most of the tegument is detached and participates in the capsid transport toward the host nucleus. Plays a role in the routing of the capsid at the nuclear pore complex and subsequent uncoating. Within the host nucleus, acts as a deneddylase and promotes the degradation of nuclear CRLs (cullin-RING ubiquitin ligases) and thereby stabilizes nuclear CRL substrates, while cytoplasmic CRLs remain unaffected. These modifications prevent host cell cycle S-phase progression and create a favorable environment allowing efficient viral genome replication. Participates later in the secondary envelopment of capsids. Indeed, plays a linker role for the association of the outer viral tegument to the capsids together with the inner tegument protein.[HAMAP-Rule:MF_04044][1] [2] [3] [4] [5] [6] [7] [8] [9]
Publication Abstract from PubMed
The tegument of all herpesviruses contains a capsid-bound large protein that is essential for multiple viral processes including capsid transport, decapsidation at the nuclear pore complex, particle assembly and secondary envelopment, through mechanisms that are still incompletely understood. We report here a structural characterization of the central 970 residues of this protein for herpes simplex virus type 1 (HSV-1 UL36, 3164 residues). This large fragment is essentially a 34 nm long monomeric fiber. The crystal structure of its C-terminus shows an elongated, domain-swapped dimer. Modeling and molecular dynamics simulations give a likely molecular organization for the monomeric form and extend our findings to alphaherpesvirinae. Hence, we propose that an essential feature of UL36 is the existence in its central region of a stalk capable of connecting capsid and membrane across the tegument and that the ability to switch between monomeric and dimeric forms may help UL36 fulfill its multiple functions.
Insights into Herpesvirus Tegument Organization from Structural Analyses of HSV-1 UL36 Central 970 Residues.,Scrima N, Lepault J, Boulard Y, Pasdeloup D, Bressanelli S, Roche S J Biol Chem. 2015 Feb 12. pii: jbc.M114.612838. PMID:25678705[10]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Schlieker C, Korbel GA, Kattenhorn LM, Ploegh HL. A deubiquitinating activity is conserved in the large tegument protein of the herpesviridae. J Virol. 2005 Dec;79(24):15582-5. PMID:16306630 doi:10.1128/JVI.79.24.15582-15585.2005
- ↑ Jovasevic V, Liang L, Roizman B. Proteolytic cleavage of VP1-2 is required for release of herpes simplex virus 1 DNA into the nucleus. J Virol. 2008 Apr;82(7):3311-9. PMID:18216103 doi:10.1128/JVI.01919-07
- ↑ Shanda SK, Wilson DW. UL36p is required for efficient transport of membrane-associated herpes simplex virus type 1 along microtubules. J Virol. 2008 Aug;82(15):7388-94. PMID:18495763 doi:10.1128/JVI.00225-08
- ↑ Roberts AP, Abaitua F, O'Hare P, McNab D, Rixon FJ, Pasdeloup D. Differing roles of inner tegument proteins pUL36 and pUL37 during entry of herpes simplex virus type 1. J Virol. 2009 Jan;83(1):105-16. PMID:18971278 doi:10.1128/JVI.01032-08
- ↑ Ko DH, Cunningham AL, Diefenbach RJ. The major determinant for addition of tegument protein pUL48 (VP16) to capsids in herpes simplex virus type 1 is the presence of the major tegument protein pUL36 (VP1/2). J Virol. 2010 Feb;84(3):1397-405. PMID:19923173 doi:10.1128/JVI.01721-09
- ↑ Gastaldello S, Hildebrand S, Faridani O, Callegari S, Palmkvist M, Di Guglielmo C, Masucci MG. A deneddylase encoded by Epstein-Barr virus promotes viral DNA replication by regulating the activity of cullin-RING ligases. Nat Cell Biol. 2010 Apr;12(4):351-61. PMID:20190741 doi:10.1038/ncb2035
- ↑ Cardone G, Newcomb WW, Cheng N, Wingfield PT, Trus BL, Brown JC, Steven AC. The UL36 tegument protein of herpes simplex virus 1 has a composite binding site at the capsid vertices. J Virol. 2012 Apr;86(8):4058-64. PMID:22345483 doi:10.1128/JVI.00012-12
- ↑ Abaitua F, Hollinshead M, Bolstad M, Crump CM, O'Hare P. A Nuclear localization signal in herpesvirus protein VP1-2 is essential for infection via capsid routing to the nuclear pore. J Virol. 2012 Sep;86(17):8998-9014. PMID:22718835 doi:10.1128/JVI.01209-12
- ↑ Sandbaumhüter M, Döhner K, Schipke J, Binz A, Pohlmann A, Sodeik B, Bauerfeind R. Cytosolic herpes simplex virus capsids not only require binding inner tegument protein pUL36 but also pUL37 for active transport prior to secondary envelopment. Cell Microbiol. 2013 Feb;15(2):248-69. PMID:23186167 doi:10.1111/cmi.12075
- ↑ Scrima N, Lepault J, Boulard Y, Pasdeloup D, Bressanelli S, Roche S. Insights into Herpesvirus Tegument Organization from Structural Analyses of HSV-1 UL36 Central 970 Residues. J Biol Chem. 2015 Feb 12. pii: jbc.M114.612838. PMID:25678705 doi:http://dx.doi.org/10.1074/jbc.M114.612838
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