6t3x

From Proteopedia

(Difference between revisions)

Current revision

Crystal structure of the truncated human cytomegalovirus pUL50-pUL53 complex

Structural highlights

6t3x is a 2 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 1.48Å
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

NEC2_HCMVA 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]NEC1_HCMVA 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_04023]^[1]

Publication Abstract from PubMed

Herpesviruses uniquely express two essential nuclear egress-regulating proteins forming a heterodimeric basic structure of the nuclear-egress complex (core NEC). These core NECs serve as a hexameric lattice-structured platform for capsid docking and recruit viral and cellular NEC-associated factors that jointly exert nuclear lamina- and membrane-rearranging functions (multicomponent NEC). Here, we report the X-ray structures of beta- and gamma-herpesvirus core NECs obtained through an innovative recombinant expression strategy based on NEC-hook::NEC-groove protein fusion constructs. This approach yielded the first structure of gamma-herpesviral core NEC, namely the 1.56 A structure of Epstein-Barr virus (EBV) BFRF1-BFLF2, as well as an increased resolution 1.48 A structure of human cytomegalovirus (HCMV) pUL50-pUL53. Detailed analysis of these structures revealed that the prominent hook segment is absolutely required for core NEC formation and contributes approx. 80% of the interaction surface of the globular domains of NEC proteins. Moreover, using HCMV::EBV hook domain swap constructs, computational prediction of the roles of individual hook residues for binding, and quantitative binding assays with synthetic peptides presenting the HCMV- and EBV-specific NEC hook sequences, we characterized the unique hook-into-groove NEC interaction at various levels. Although the overall physicochemical characteristics of the protein interfaces differ considerably in these beta- and gamma-herpesvirus NECs, the binding free energy contributions of residues displayed from identical positions are similar. In summary, the results of our study reveal critical details of the molecular mechanism of herpesviral NEC interactions and highlight their potential as an antiviral drug target.

High-resolution crystal structures of two prototypical beta- and gamma-herpesviral nuclear egress complexes unravel the determinants of subfamily specificity.,Muller YA, Hage S, Alkhashrom S, Hollriegl T, Weigert S, Dolles S, Hof K, Walzer SA, Egerer-Sieber C, Conrad M, Holst S, Losing J, Sonntag E, Sticht H, Eichler J, Marschall M J Biol Chem. 2020 Jan 24. pii: RA119.011546. doi: 10.1074/jbc.RA119.011546. PMID:31980459^[2]

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

References

↑ Sharma M, Bender BJ, Kamil JP, Lye MF, Pesola JM, Reim NI, Hogle JM, Coen DM. Human cytomegalovirus UL97 phosphorylates the viral nuclear egress complex. J Virol. 2015 Jan;89(1):523-34. PMID:25339763 doi:10.1128/JVI.02426-14
↑ Muller YA, Hage S, Alkhashrom S, Hollriegl T, Weigert S, Dolles S, Hof K, Walzer SA, Egerer-Sieber C, Conrad M, Holst S, Losing J, Sonntag E, Sticht H, Eichler J, Marschall M. High-resolution crystal structures of two prototypical beta- and gamma-herpesviral nuclear egress complexes unravel the determinants of subfamily specificity. J Biol Chem. 2020 Jan 24. pii: RA119.011546. doi: 10.1074/jbc.RA119.011546. PMID:31980459 doi:http://dx.doi.org/10.1074/jbc.RA119.011546

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/6t3x"

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

@@ Line 3: / Line 3: @@
 <StructureSection load='6t3x' size='340' side='right'caption='[[6t3x]], [[Resolution|resolution]] 1.48&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6t3x]] 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=6T3X OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6T3X FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6t3x]] 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=6T3X OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6T3X FirstGlance]. <br>
-</td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">NEC1, UL53 ([http://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]] 1.48&#8491;</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=6t3x FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6t3x OCA], [http://pdbe.org/6t3x PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6t3x RCSB], [http://www.ebi.ac.uk/pdbsum/6t3x PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6t3x 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=6t3x FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6t3x OCA], [https://pdbe.org/6t3x PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6t3x RCSB], [https://www.ebi.ac.uk/pdbsum/6t3x PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6t3x ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[http://www.uniprot.org/uniprot/NEC2_HCMVA NEC2_HCMVA]] 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]
+[https://www.uniprot.org/uniprot/NEC2_HCMVA NEC2_HCMVA] 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][https://www.uniprot.org/uniprot/NEC1_HCMVA NEC1_HCMVA] 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_04023]<ref>PMID:25339763</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: Fusion protein]]
-[[Category: Nuclear egress]]
-[[Category: Viral protein]]

6t3x

From Proteopedia

Current revision

Crystal structure of the truncated human cytomegalovirus pUL50-pUL53 complex

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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