6gg0
Cryo-EM structure of BK polyomavirus like particle in complex with single chain antibody ScFv41F17
Structural highlights
FunctionVP1_POVBK Forms an icosahedral capsid with a T=7 symmetry and a 50 nm diameter. The capsid is composed of 72 pentamers linked to each other by disulfide bonds and associated with VP2 or VP3 proteins. Interacts with gangliosides GT1b and GD1b containing terminal alpha(2-8)-linked sialic acids on the cell surface to provide virion attachment to target cell. This attachment induces virion internalization predominantly through caveolin-mediated endocytosis and traffics to the endoplasmic reticulum. Inside the endoplasmic reticulum, the protein folding machinery isomerizes VP1 interpentamer disulfide bonds, thereby triggering initial uncoating. Next, the virion uses the endoplasmic reticulum-associated degradation machinery to probably translocate in the cytosol before reaching the nucleus. Nuclear entry of the viral DNA involves the selective exposure and importin recognition of VP2/Vp3 nuclear localization signal. In late phase of infection, neo-synthesized VP1 encapsulates replicated genomic DNA in the nucleus, and participates in rearranging nucleosomes around the viral DNA (By similarity).[1] [2] Publication Abstract from PubMedHuman polyomaviruses cause a common childhood infection worldwide and typically elicit a neutralizing antibody and cellular immune response, while establishing a dormant infection in the kidney with minimal clinical manifestations. However, viral reactivation can cause severe pathology in immunocompromised individuals. We developed a high-throughput, functional antibody screen to examine the humoral response to BK polyomavirus. This approach enabled the isolation of antibodies from all peripheral B cell subsets and revealed the anti-BK virus antibody repertoire as clonally complex with respect to immunoglobulin sequences and isotypes (both IgM and IgG), including a high frequency of monoclonal antibodies that broadly neutralize BK virus subtypes and the related JC polyomavirus. Cryo-electron microscopy of a broadly neutralizing IgG single-chain variable fragment complexed with BK virus-like particles revealed the quaternary nature of a conserved viral epitope at the junction between capsid pentamers. These features unravel a potent modality for inhibiting polyomavirus infection in kidney transplant recipients and other immunocompromised patients. Human Memory B Cells Harbor Diverse Cross-Neutralizing Antibodies against BK and JC Polyomaviruses.,Lindner JM, Cornacchione V, Sathe A, Be C, Srinivas H, Riquet E, Leber XC, Hein A, Wrobel MB, Scharenberg M, Pietzonka T, Wiesmann C, Abend J, Traggiai E Immunity. 2019 Feb 16. pii: S1074-7613(19)30048-2. doi:, 10.1016/j.immuni.2019.02.003. PMID:30824324[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
| ||||||||||||||
