| Structural highlights
Function
[TRX1_HCMVA] 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. [PP150_HCMVA] Participates in the last steps of viral maturation and release. Associates with nuclear capsids prior to DNA encapsidation and later preserves the integrity of nucleocapsids through secondary envelopment at the assembly compartment. Interacts with host CCNA2 and thereby blocks the onset of lytic gene expression to promote establishment of a quiescent state of infection in undifferentiated cells.[1] [2] [3] [4] [5] [SCP_HCMVA] 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. [MCP_HCMVA] 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. [TRX2_HCMVA] 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.
Publication Abstract from PubMed
Herpesviruses possess a genome-pressurized capsid. The 235-kilobase genome of human cytomegalovirus (HCMV) is by far the largest of any herpesvirus, yet it has been unclear how its capsid, which is similar in size to those of other herpesviruses, is stabilized. Here we report a HCMV atomic structure consisting of the herpesvirus-conserved capsid proteins MCP, Tri1, Tri2, and SCP and the HCMV-specific tegument protein pp150-totaling ~4000 molecules and 62 different conformers. MCPs manifest as a complex of insertions around a bacteriophage HK97 gp5-like domain, which gives rise to three classes of capsid floor-defining interactions; triplexes, composed of two "embracing" Tri2 conformers and a "third-wheeling" Tri1, fasten the capsid floor. HCMV-specific strategies include using hexon channels to accommodate the genome and pp150 helix bundles to secure the capsid via cysteine tetrad-to-SCP interactions. Our structure should inform rational design of countermeasures against HCMV, other herpesviruses, and even HIV/AIDS.
Atomic structure of the human cytomegalovirus capsid with its securing tegument layer of pp150.,Yu X, Jih J, Jiang J, Zhou ZH Science. 2017 Jun 30;356(6345). pii: eaam6892. doi: 10.1126/science.aam6892. PMID:28663444[6]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ AuCoin DP, Smith GB, Meiering CD, Mocarski ES. Betaherpesvirus-conserved cytomegalovirus tegument protein ppUL32 (pp150) controls cytoplasmic events during virion maturation. J Virol. 2006 Aug;80(16):8199-210. PMID:16873276 doi:http://dx.doi.org/10.1128/JVI.00457-06
- ↑ Tandon R, Mocarski ES. Control of cytoplasmic maturation events by cytomegalovirus tegument protein pp150. J Virol. 2008 Oct;82(19):9433-44. doi: 10.1128/JVI.00533-08. Epub 2008 Jul 23. PMID:18653449 doi:http://dx.doi.org/10.1128/JVI.00533-08
- ↑ Indran SV, Britt WJ. A role for the small GTPase Rab6 in assembly of human cytomegalovirus. J Virol. 2011 May;85(10):5213-9. doi: 10.1128/JVI.02605-10. Epub 2011 Mar 16. PMID:21411515 doi:http://dx.doi.org/10.1128/JVI.02605-10
- ↑ Dai X, Yu X, Gong H, Jiang X, Abenes G, Liu H, Shivakoti S, Britt WJ, Zhu H, Liu F, Zhou ZH. The smallest capsid protein mediates binding of the essential tegument protein pp150 to stabilize DNA-containing capsids in human cytomegalovirus. PLoS Pathog. 2013 Aug;9(8):e1003525. doi: 10.1371/journal.ppat.1003525. Epub 2013, Aug 15. PMID:23966856 doi:http://dx.doi.org/10.1371/journal.ppat.1003525
- ↑ Bogdanow B, Weisbach H, von Einem J, Straschewski S, Voigt S, Winkler M, Hagemeier C, Wiebusch L. Human cytomegalovirus tegument protein pp150 acts as a cyclin A2-CDK-dependent sensor of the host cell cycle and differentiation state. Proc Natl Acad Sci U S A. 2013 Oct 22;110(43):17510-5. doi:, 10.1073/pnas.1312235110. Epub 2013 Oct 7. PMID:24101496 doi:http://dx.doi.org/10.1073/pnas.1312235110
- ↑ Yu X, Jih J, Jiang J, Zhou ZH. Atomic structure of the human cytomegalovirus capsid with its securing tegument layer of pp150. Science. 2017 Jun 30;356(6345). pii: eaam6892. doi: 10.1126/science.aam6892. PMID:28663444 doi:http://dx.doi.org/10.1126/science.aam6892
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