Structural highlights
Function
[D0UZN7_HHV8] 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] [Q76RF6_HHV8] 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_04018] [Q76RH8_HHV8] Capsid vertex-specific component that plays a role during viral DNA encapsidation, assuring correct genome cleavage and presumably stabilizing capsids that contain full-length viral genomes.[HAMAP-Rule:MF_04017] [LTP_HHV8P] 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] [Q76RF4_HHV8] 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_04022] [Q76RI7_HHV8] Capsid vertex-specific component that plays a role during viral DNA encapsidation, assuring correct genome cleavage and presumably stabilizing capsids that contain full-length viral genomes. Participates in the interaction between the capsid and the tegument through interaction with the large tegument protein/LTP.[HAMAP-Rule:MF_04025] [C7E5A9_HHV8] 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
Assembly of Kaposi's sarcoma-associated herpesvirus (KSHV) begins at a bacteriophage-like portal complex that nucleates formation of an icosahedral capsid with capsid-associated tegument complexes (CATCs) and facilitates translocation of an approximately 150-kb dsDNA genome, followed by acquisition of a pleomorphic tegument and envelope. Because of deviation from icosahedral symmetry, KSHV portal and tegument structures have largely been obscured in previous studies. Using symmetry-relaxed cryo-EM, we determined the in situ structure of the KSHV portal and its interactions with surrounding capsid proteins, CATCs, and the terminal end of KSHV's dsDNA genome. Our atomic models of the portal and capsid/CATC, together with visualization of CATCs' variable occupancy and alternate orientation of CATC-interacting vertex triplexes, suggest a mechanism whereby the portal orchestrates procapsid formation and asymmetric long-range determination of CATC attachment during DNA packaging prior to pleomorphic tegumentation/envelopment. Structure-based mutageneses confirm that a triplex deep binding groove for CATCs is a hotspot that holds promise for antiviral development.
DNA-Packing Portal and Capsid-Associated Tegument Complexes in the Tumor Herpesvirus KSHV.,Gong D, Dai X, Jih J, Liu YT, Bi GQ, Sun R, Zhou ZH Cell. 2019 Sep 5;178(6):1329-1343.e12. doi: 10.1016/j.cell.2019.07.035. Epub 2019, Aug 22. PMID:31447177[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Gonzalez CM, Wang L, Damania B. Kaposi's sarcoma-associated herpesvirus encodes a viral deubiquitinase. J Virol. 2009 Oct;83(19):10224-33. doi: 10.1128/JVI.00589-09. Epub 2009 Jul 29. PMID:19640989 doi:http://dx.doi.org/10.1128/JVI.00589-09
- ↑ Gong D, Dai X, Jih J, Liu YT, Bi GQ, Sun R, Zhou ZH. DNA-Packing Portal and Capsid-Associated Tegument Complexes in the Tumor Herpesvirus KSHV. Cell. 2019 Sep 5;178(6):1329-1343.e12. doi: 10.1016/j.cell.2019.07.035. Epub 2019, Aug 22. PMID:31447177 doi:http://dx.doi.org/10.1016/j.cell.2019.07.035
