6igc | pdb_00006igc
Crystal structure of HPV58/33/52 chimeric L1 pentamer
Structural highlights
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Function[VL1_HPV58] 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 L2 proteins. Binds to heparan sulfate proteoglycans on cell surface of basal layer keratinocytes to provide initial virion attachment. This binding mediates a conformational change in the virus capsid that facilitates efficient infection. The virion enters the host cell via endocytosis. During virus trafficking, L1 protein dissociates from the viral DNA and the genomic DNA is released to the host nucleus. The virion assembly takes place within the cell nucleus. Encapsulates the genomic DNA together with protein L2.[HAMAP-Rule:MF_04002][1] Publication Abstract from PubMedSequence variability in surface-antigenic sites of pathogenic proteins is an important obstacle in vaccine development. Over 200 distinct genomic sequences have been identified for human papillomavirus (HPV), of which more than 18 are associated with cervical cancer. Here, based on the high structural similarity of L1 surface loops within a group of phylogenetically close HPV types, we design a triple-type chimera of HPV33/58/52 using loop swapping. The chimeric VLPs elicit neutralization titers comparable with a mix of the three wild-type VLPs both in mice and non-human primates. This engineered region of the chimeric protein recapitulates the conformational contours of the antigenic surfaces of the parental-type proteins, offering a basis for this high immunity. Our stratagem is equally successful in developing other triplet-type chimeras (HPV16/35/31, HPV56/66/53, HPV39/68/70, HPV18/45/59), paving the way for the development of an improved HPV prophylactic vaccine against all carcinogenic HPV strains. This technique may also be extrapolated to other microbes. Rational design of a triple-type human papillomavirus vaccine by compromising viral-type specificity.,Li Z, Song S, He M, Wang D, Shi J, Liu X, Li Y, Chi X, Wei S, Yang Y, Wang Z, Li J, Qian H, Yu H, Zheng Q, Yan X, Zhao Q, Zhang J, Gu Y, Li S, Xia N Nat Commun. 2018 Dec 18;9(1):5360. doi: 10.1038/s41467-018-07199-6. PMID:30560935[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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