6nhj

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(Difference between revisions)

Revision as of 04:38, 5 March 2020

Atomic structures and deletion mutant reveal different capsid-binding patterns and functional significance of tegument protein pp150 in murine and human cytomegaloviruses with implications for therapeutic development

6nhj, resolution 5.00Å

Structural highlights

6nhj is a 55 chain structure with sequence from Murine cytomegalovirus (strain smith). Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Experimental data:	Check to display Experimental Data
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[A0A1S5YGR4_MUHV1] Self-assembles to form an icosahedral capsid with a T=16 symmetry, about 200 nm in diameter, and consisting of 150 hexons and 12 pentons (total of 162 capsomers). Hexons form the edges and faces of the capsid and are each composed of six MCP molecules. In contrast, one penton is found at each of the 12 vertices. Eleven of the pentons are MCP pentamers, while the last vertex is occupied by the portal complex. The capsid is surrounded by a layer of proteinaceous material designated the tegument which, in turn, is enclosed in an envelope of host cell-derived lipids containing virus-encoded glycoproteins.[HAMAP-Rule:MF_04016] [D3XDN6_MUHVS] Participates in the assembly of the infectious particles by decorating the outer surface of the capsid shell and thus forming a layer between the capsid and the tegument. Complexes composed of the major capsid protein and small capsomere-interacting protein/SCP assemble together in the host cytoplasm and are translocated to the nucleus, where they accumulate and participate in capsid assembly.[HAMAP-Rule:MF_04021] [D3XDR2_MUHVS] Structural component of the T=16 icosahedral capsid. The capsid is composed of pentamers and hexamers of major capsid protein/MCP, which are linked together by heterotrimers called triplexes. These triplexes are formed by a single molecule of triplex protein 1/TRX1 and two copies of triplex protein 2/TRX2. Additionally, TRX1 is required for efficient transport of TRX2 to the nucleus, which is the site of capsid assembly.[HAMAP-Rule:MF_04019]

Publication Abstract from PubMed

Cytomegalovirus (CMV) infection causes birth defects and life-threatening complications in immunosuppressed patients. Lack of vaccine and need for more effective drugs have driven widespread ongoing therapeutic development efforts against human CMV (HCMV), mostly using murine CMV (MCMV) as the model system for preclinical animal tests. The recent publication (Yu et al., 2017, DOI: 10.1126/science.aam6892) of an atomic model for HCMV capsid with associated tegument protein pp150 has infused impetus for rational design of novel vaccines and drugs, but the absence of high-resolution structural data on MCMV remains a significant knowledge gap in such development efforts. Here, by cryoEM with sub-particle reconstruction method, we have obtained the first atomic structure of MCMV capsid with associated pp150. Surprisingly, the capsid-binding patterns of pp150 differ between HCMV and MCMV despite their highly similar capsid structures. In MCMV, pp150 is absent on triplex Tc and exists as a "Lambda"-shaped dimer on other triplexes, leading to only 260 groups of two pp150 subunits per capsid in contrast to 320 groups of three pp150 subunits each in a "Delta"-shaped fortifying configuration. Many more amino acids contribute to pp150-pp150 interactions in MCMV than in HCMV, making MCMV pp150 dimer inflexible thus incompatible to instigate triplex Tc-binding as observed in HCMV. While pp150 is essential in HCMV, our pp150-deletion mutant of MCMV remained viable though with attenuated infectivity and exhibiting defects in retaining viral genome. These results thus invalidate targeting pp150, but lend support to targeting capsid proteins, when using MCMV as a model for HCMV pathogenesis and therapeutic studies.

Atomic structures and deletion mutant reveal different capsid-binding patterns and functional significance of tegument protein pp150 in murine and human cytomegaloviruses with implications for therapeutic development.,Liu W, Dai X, Jih J, Chan K, Trang P, Yu X, Balogun R, Mei Y, Liu F, Zhou ZH PLoS Pathog. 2019 Feb 19;15(2):e1007615. doi: 10.1371/journal.ppat.1007615., eCollection 2019 Feb. PMID:30779794^[1]

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

References

↑ Liu W, Dai X, Jih J, Chan K, Trang P, Yu X, Balogun R, Mei Y, Liu F, Zhou ZH. Atomic structures and deletion mutant reveal different capsid-binding patterns and functional significance of tegument protein pp150 in murine and human cytomegaloviruses with implications for therapeutic development. PLoS Pathog. 2019 Feb 19;15(2):e1007615. doi: 10.1371/journal.ppat.1007615., eCollection 2019 Feb. PMID:30779794 doi:http://dx.doi.org/10.1371/journal.ppat.1007615

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/6nhj"

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 ==Atomic structures and deletion mutant reveal different capsid-binding patterns and functional significance of tegument protein pp150 in murine and human cytomegaloviruses with implications for therapeutic development==
-<StructureSection load='6nhj' size='340' side='right'caption='[[6nhj]], [[Resolution|resolution]] 5.00&Aring;' scene=''>
+<SX load='6nhj' size='340' side='right' viewer='molstar' caption='[[6nhj]], [[Resolution|resolution]] 5.00&Aring;' scene=''>
 == Structural highlights ==
 <table><tr><td colspan='2'>[[6nhj]] is a 55 chain structure with sequence from [http://en.wikipedia.org/wiki/Murine_cytomegalovirus_(strain_smith) Murine cytomegalovirus (strain smith)]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6NHJ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6NHJ FirstGlance]. <br>
@@ Line 20: / Line 20: @@
 <references/>
 __TOC__
-</StructureSection>
+</SX>
 [[Category: Large Structures]]
 [[Category: Balogun, R]]

6nhj

From Proteopedia

Revision as of 04:38, 5 March 2020

Atomic structures and deletion mutant reveal different capsid-binding patterns and functional significance of tegument protein pp150 in murine and human cytomegaloviruses with implications for therapeutic development

Structural highlights

Function

Publication Abstract from PubMed

References

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