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| | <StructureSection load='5d5n' size='340' side='right'caption='[[5d5n]], [[Resolution|resolution]] 2.44Å' scene=''> | | <StructureSection load='5d5n' size='340' side='right'caption='[[5d5n]], [[Resolution|resolution]] 2.44Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5d5n]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Hcmva Hcmva]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5D5N OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5D5N FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5d5n]] is a 2 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=5D5N OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5D5N FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</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]] 2.44Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">UL50 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10360 HCMVA]), UL53 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10360 HCMVA])</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</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=5d5n FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5d5n OCA], [http://pdbe.org/5d5n PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5d5n RCSB], [http://www.ebi.ac.uk/pdbsum/5d5n PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5d5n 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=5d5n FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5d5n OCA], [https://pdbe.org/5d5n PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5d5n RCSB], [https://www.ebi.ac.uk/pdbsum/5d5n PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5d5n ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/UL50_HCMVA UL50_HCMVA]] Plays a major role in virion nuclear egress, the first step of virion release from infected cell. Viral capsids are initially assembled within the nucleus, UL53/UL50 complex induces capsids budding and envelopment into the perinuclear space. Then UL53/UL50 complex promotes fusion of perinuclear virion envelope with the outer nuclear membrane, releasing viral capsid into the cytoplasm where it will engages budding sites in the Golgi or trans-Golgi network (By similarity). [[http://www.uniprot.org/uniprot/UL53_HCMVA UL53_HCMVA]] Plays a major role in virion nuclear egress, the first step of virion release from infected cell. Viral capsids are initially assembled within the nucleus, UL53/UL50 complex induces capsids budding and envelopment into the perinuclear space. Then UL53/UL50 complex promotes fusion of perinuclear virion envelope with the outer nuclear membrane, releasing viral capsid into the cytoplasm where it will engages budding sites in the Golgi or trans-Golgi network (By similarity). | + | [https://www.uniprot.org/uniprot/NEC2_HCMVM NEC2_HCMVM] Plays an essential role in virion nuclear egress, the first step of virion release from infected cell. Within the host nucleus, NEC1 interacts with the newly formed capsid through the vertexes and directs it to the inner nuclear membrane by associating with NEC2. Induces the budding of the capsid at the inner nuclear membrane as well as its envelopment into the perinuclear space. There, the NEC1/NEC2 complex promotes the fusion of the enveloped capsid with the outer nuclear membrane and the subsequent release of the viral capsid into the cytoplasm where it will reach the secondary budding sites in the host Golgi or trans-Golgi network.[HAMAP-Rule:MF_04024] |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Hcmva]] | + | [[Category: Human herpesvirus 5 strain AD169]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Egerer-Sieber, C]] | + | [[Category: Egerer-Sieber C]] |
| - | [[Category: Hohl, K]] | + | [[Category: Hohl K]] |
| - | [[Category: Muller, Y A]] | + | [[Category: Muller YA]] |
| - | [[Category: Sevvana, M]] | + | [[Category: Sevvana M]] |
| - | [[Category: Walzer, S A]] | + | [[Category: Walzer SA]] |
| - | [[Category: Viral nuclear egress complex]]
| + | |
| - | [[Category: Viral protein]]
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| Structural highlights
Function
NEC2_HCMVM Plays an essential role in virion nuclear egress, the first step of virion release from infected cell. Within the host nucleus, NEC1 interacts with the newly formed capsid through the vertexes and directs it to the inner nuclear membrane by associating with NEC2. Induces the budding of the capsid at the inner nuclear membrane as well as its envelopment into the perinuclear space. There, the NEC1/NEC2 complex promotes the fusion of the enveloped capsid with the outer nuclear membrane and the subsequent release of the viral capsid into the cytoplasm where it will reach the secondary budding sites in the host Golgi or trans-Golgi network.[HAMAP-Rule:MF_04024]
Publication Abstract from PubMed
Nuclear replication of cytomegalovirus relies on elaborate mechanisms of nucleocytoplasmic egress of viral particles. Hereby, the role of two essential and conserved viral nuclear egress proteins pUL50 and pUL53 is pivotal. pUL50 and pUL53 heterodimerize and form a core nuclear egress complex (NEC), which is anchored to the inner nuclear membrane and provides a scaffold for the assembly of a multimeric viral-cellular NEC. Here, we report the crystal structure of the pUL50-pUL53 heterodimer (amino acids 1-175 and 50-292, respectively) at 2.44 A resolution. Both proteins adopt a globular fold with mixed alpha and beta secondary structure elements. pUL53-specific features include a zinc-binding site and a hook-like N-terminal extension, the latter representing a hallmark element of the pUL50-pUL53 interaction. The hook-like extension (amino acids 60-87) embraces pUL50 and contributes 1390 A2 to the total interface area (1780 A2). The pUL50 structure overall resembles the recently published NMR structure of the murine cytomegalovirus homolog pM50 but reveals a considerable repositioning of the very C-terminal alpha-helix of pUL50 upon pUL53 binding. pUL53 shows structural resemblance with the GHKL domain of bacterial sensory histidine kinases. A close examination of the crystal structure indicates partial assembly of pUL50-pUL53 heterodimers to hexameric ring-like structures possibly providing additional scaffolding opportunities for NEC. Combined, the structural information on pUL50-pUL53 considerably improves our understanding of the mechanism of HCMV nuclear egress. It may also accelerate the validation of the NEC as a unique target for developing a novel type of antiviral drugs and improved options of broad-spectrum antiherpesviral therapy.
Crystal Structure of the Human Cytomegalovirus pUL50-pUL53 Core Nuclear Egress Complex Provides Insight into a Unique Assembly Scaffold for Virus-Host Protein Interactions.,Walzer SA, Egerer-Sieber C, Sticht H, Sevvana M, Hohl K, Milbradt J, Muller YA, Marschall M J Biol Chem. 2015 Oct 2. pii: jbc.C115.686527. PMID:26432641[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Walzer SA, Egerer-Sieber C, Sticht H, Sevvana M, Hohl K, Milbradt J, Muller YA, Marschall M. Crystal Structure of the Human Cytomegalovirus pUL50-pUL53 Core Nuclear Egress Complex Provides Insight into a Unique Assembly Scaffold for Virus-Host Protein Interactions. J Biol Chem. 2015 Oct 2. pii: jbc.C115.686527. PMID:26432641 doi:http://dx.doi.org/10.1074/jbc.C115.686527
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