| Structural highlights
5vob is a 7 chain structure with sequence from Hcmv8, Hcmva, Hcmvm and Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Ligands: | , |
| Related: | 5voc, 5vod |
| Gene: | gH, UL75 (HCMVM), gL, UL115 (HCMV8), UL128 (HCMVA), UL130 (HCMVM), UL131A (HCMVM), IGKV3-15 (HUMAN) |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
[GL_HCMV8] The heterodimer glycoprotein H-glycoprotein L is required for the fusion of viral and plasma membranes leading to virus entry into the host cell. Acts as a functional inhibitor of gH and maintains gH in an inhibited form. Upon binding to host integrins, gL dissociates from gH leading to activation of the viral fusion glycoproteins gB and gH. [GH_HCMVM] The heterodimer glycoprotein H-glycoprotein L is required for the fusion of viral and plasma membranes leading to virus entry into the host cell. Following initial binding to host receptor, membrane fusion is mediated by the fusion machinery composed of gB and the heterodimer gH/gL. May also be involved in the fusion between the virion envelope and the outer nuclear membrane during virion morphogenesis. [U131A_HCMVM] Plays an essential role in endothelial cell entry and release steps. Contributes to the formation of the complex between UL128, UL130 and gH-gL.[1] [2]
Publication Abstract from PubMed
Human cytomegalovirus (HCMV) is the leading viral cause of birth defects and organ transplant rejection. The HCMV gH/gL/UL128/UL130/UL131A complex (Pentamer) is the main target of humoral responses and thus a key vaccine candidate. We report two structures of Pentamer bound to human neutralizing antibodies, 8I21 and 9I6, at 3.0 and 5.9 A resolution, respectively. The HCMV gH/gL architecture is similar to that of Epstein-Barr virus (EBV) except for amino-terminal extensions on both subunits. The extension of gL forms a subdomain composed of a three-helix bundle and a beta hairpin that acts as a docking site for UL128/UL130/UL131A. Structural analysis reveals that Pentamer is a flexible molecule, and suggests sites for engineering stabilizing mutations. We also identify immunogenic surfaces important for cellular interactions by epitope mapping and functional assays. These results can guide the development of effective vaccines and immunotherapeutics against HCMV.
Structural basis for potent antibody-mediated neutralization of human cytomegalovirus.,Chandramouli S, Malito E, Nguyen T, Luisi K, Donnarumma D, Xing Y, Norais N, Yu D, Carfi A Sci Immunol. 2017 Jun 30;2(12). pii: eaan1457. doi: 10.1126/sciimmunol.aan1457. PMID:28783665[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Adler B, Scrivano L, Ruzcics Z, Rupp B, Sinzger C, Koszinowski U. Role of human cytomegalovirus UL131A in cell type-specific virus entry and release. J Gen Virol. 2006 Sep;87(Pt 9):2451-60. PMID:16894182 doi:http://dx.doi.org/10.1099/vir.0.81921-0
- ↑ Schuessler A, Sampaio KL, Straschewski S, Sinzger C. Mutational mapping of pUL131A of human cytomegalovirus emphasizes its central role for endothelial cell tropism. J Virol. 2012 Jan;86(1):504-12. doi: 10.1128/JVI.05354-11. Epub 2011 Oct 26. PMID:22031943 doi:http://dx.doi.org/10.1128/JVI.05354-11
- ↑ Chandramouli S, Malito E, Nguyen T, Luisi K, Donnarumma D, Xing Y, Norais N, Yu D, Carfi A. Structural basis for potent antibody-mediated neutralization of human cytomegalovirus. Sci Immunol. 2017 Jun 30;2(12). pii: eaan1457. doi: 10.1126/sciimmunol.aan1457. PMID:28783665 doi:http://dx.doi.org/10.1126/sciimmunol.aan1457
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