3j8v

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Cryo-EM reconstruction of quasi-HPV16 complex with H16.14J Fab

3j8v, resolution 13.90Å

Structural highlights

3j8v is a 13 chain structure with sequence from Human papillomavirus type 16 and Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	Electron Microscopy, Resolution 13.9Å
Experimental data:	Check to display Experimental Data
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

VL1_HPV16 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] ^[2] ^[3]

Publication Abstract from PubMed

Cryo-electron microscopy (cryo-EM) was used to solve the structures of human papillomavirus type 16 (HPV16) complexed with fragments of antibody (Fab) from three different neutralizing monoclonals (mAbs): H16.1A, H16.14J, and H263.A2. The structure-function analysis revealed predominantly monovalent binding of each Fab with capsid interactions that involved multiple loops from symmetry related copies of the major capsid protein. The residues identified in each Fab-virus interface map to a conformational groove on the surface of the capsomer. In addition to the known involvement of the FG and HI loops, the DE loop was also found to constitute the core of each epitope. Surprisingly, the epitope mapping also identified minor contributions by EF and BC loops. Complementary immunological assays included mAb and Fab neutralization. The specific binding characteristics of mAbs correlated with different neutralizing behaviors in pre- and post-attachment neutralization assays.

Structural comparison of four different antibodies interacting with human papillomavirus 16 and mechanisms of neutralization.,Guan J, Bywaters SM, Brendle SA, Lee H, Ashley RE, Makhov AM, Conway JF, Christensen ND, Hafenstein S Virology. 2015 May 18;483:253-263. doi: 10.1016/j.virol.2015.04.016. PMID:25996608^[4]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Bousarghin L, Touze A, Sizaret PY, Coursaget P. Human papillomavirus types 16, 31, and 58 use different endocytosis pathways to enter cells. J Virol. 2003 Mar;77(6):3846-50. PMID:12610160
↑ Surviladze Z, Sterkand RT, Ozbun MA. Interaction of human papillomavirus type 16 particles with heparan sulfate and syndecan-1 molecules in the keratinocyte extracellular matrix plays an active role in infection. J Gen Virol. 2015 Aug;96(8):2232-41. doi: 10.1099/vir.0.000147. PMID:26289843 doi:http://dx.doi.org/10.1099/vir.0.000147
↑ Heino P, Dillner J, Schwartz S. Human papillomavirus type 16 capsid proteins produced from recombinant Semliki Forest virus assemble into virus-like particles. Virology. 1995 Dec 20;214(2):349-59. PMID:8553535 doi:http://dx.doi.org/10.1006/viro.1995.0044
↑ Guan J, Bywaters SM, Brendle SA, Lee H, Ashley RE, Makhov AM, Conway JF, Christensen ND, Hafenstein S. Structural comparison of four different antibodies interacting with human papillomavirus 16 and mechanisms of neutralization. Virology. 2015 May 18;483:253-263. doi: 10.1016/j.virol.2015.04.016. PMID:25996608 doi:http://dx.doi.org/10.1016/j.virol.2015.04.016