8ah0 | pdb_00008ah0
BK Polyomavirus VP1 mutant VQQ
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 PubMedBK polyomavirus (BKPyV) is an opportunistic pathogen that uses the b-series gangliosides GD1b and GT1b as entry receptors. Here, we characterize the impact of naturally occurring VP1 mutations on ganglioside binding, VP1 protein structure, and virus tropism. Infectious entry of single mutants E73Q and E73A and the triple mutant A72V-E73Q-E82Q (VQQ) remains sialic acid dependent, and all three variants acquire binding to a-series gangliosides, including GD1a. However, the E73A and VQQ variants lose the ability to infect ganglioside-complemented cells, and this correlates with a clear shift of the BC2 loop in the crystal structures of E73A and VQQ. On the other hand, the K69N mutation in the K69N-E82Q variant leads to a steric clash that precludes sialic acid binding. Nevertheless, this mutant retains significant infectivity in 293TT cells, which is not dependent on heparan sulfate proteoglycans, implying that an unknown sialic acid-independent entry receptor for BKPyV exists. Structural and functional analysis of natural capsid variants suggests sialic acid-independent entry of BK polyomavirus.,Sorin MN, Di Maio A, Silva LM, Ebert D, Delannoy CP, Nguyen NK, Guerardel Y, Chai W, Halary F, Renaudin-Autain K, Liu Y, Bressollette-Bodin C, Stehle T, McIlroy D Cell Rep. 2023 Feb 14;42(2):112114. doi: 10.1016/j.celrep.2023.112114. PMID:36790933[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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