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Maturation of the human papillomavirus 16 capsid.

Cardone G, Moyer AL, Cheng N, Thompson CD, Dvoretzky I, Lowy DR, Schiller JT, Steven AC, Buck CB, Trus BL - MBio (2014)

Bottom Line: A C175S mutant that cannot achieve normal inter-L1 disulfide cross-links shows maturation-related shrinkage but does not achieve the fully condensed 60-nm form.HPV types associated with a high risk of cancer, such as HPV16, are generally transmitted via sexual contact.The availability of a pseudoatomic model of the fully mature HPV16 virion should help guide understanding of antibody responses elicited by HPV capsid-based vaccines.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Structural Biology, National Institute for Arthritis, Musculoskeletal and Skin Diseases, National Institutes of Health (NIH), Bethesda, Maryland, USA.

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Related in: MedlinePlus

Computer analysis of the capsids allowed to mature for 18 h provided a 3D reconstruction of mature HPV16 capsids (a) as well as two slightly larger, presumably less mature capsids (b and c). All images have had their internal DNA computationally removed in order to visualize the protein capsid. The mature capsid (a) contained 1,026 images and has a nominal diameter of 600 Å. The next capsid class (b) contained 1,106 images and has a 610-Å diameter. The least mature capsid (c) contained 1,296 images and has a 626-Å diameter. Bar = 200 Å.
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fig2: Computer analysis of the capsids allowed to mature for 18 h provided a 3D reconstruction of mature HPV16 capsids (a) as well as two slightly larger, presumably less mature capsids (b and c). All images have had their internal DNA computationally removed in order to visualize the protein capsid. The mature capsid (a) contained 1,026 images and has a nominal diameter of 600 Å. The next capsid class (b) contained 1,106 images and has a 610-Å diameter. The least mature capsid (c) contained 1,296 images and has a 626-Å diameter. Bar = 200 Å.

Mentions: Micrographs of gel-filtered capsids that had been allowed to mature for 18 h showed predominantly the familiar 60-nm capsid form (Fig. 1a). However, capsids with larger diameters were also observed (roughly 3 to 5%). Analyzing 7,823 capsid images from 16 micrographs, we were able to obtain three classes of various sizes from 600 Å to 626 Å (Fig. 2), presumably corresponding to the final stages in the maturation of HPV. Although a subpopulation of even larger capsid species was visible in some images, iterative refinement of all images against four size classes of images resulted in two of the classes merging, yielding only 3 classes (as before). This could be due to the limited number of images in the larger size class, or it might simply indicate that the larger classes are too irregular to be accommodated in an icosahedral model.


Maturation of the human papillomavirus 16 capsid.

Cardone G, Moyer AL, Cheng N, Thompson CD, Dvoretzky I, Lowy DR, Schiller JT, Steven AC, Buck CB, Trus BL - MBio (2014)

Computer analysis of the capsids allowed to mature for 18 h provided a 3D reconstruction of mature HPV16 capsids (a) as well as two slightly larger, presumably less mature capsids (b and c). All images have had their internal DNA computationally removed in order to visualize the protein capsid. The mature capsid (a) contained 1,026 images and has a nominal diameter of 600 Å. The next capsid class (b) contained 1,106 images and has a 610-Å diameter. The least mature capsid (c) contained 1,296 images and has a 626-Å diameter. Bar = 200 Å.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4128349&req=5

fig2: Computer analysis of the capsids allowed to mature for 18 h provided a 3D reconstruction of mature HPV16 capsids (a) as well as two slightly larger, presumably less mature capsids (b and c). All images have had their internal DNA computationally removed in order to visualize the protein capsid. The mature capsid (a) contained 1,026 images and has a nominal diameter of 600 Å. The next capsid class (b) contained 1,106 images and has a 610-Å diameter. The least mature capsid (c) contained 1,296 images and has a 626-Å diameter. Bar = 200 Å.
Mentions: Micrographs of gel-filtered capsids that had been allowed to mature for 18 h showed predominantly the familiar 60-nm capsid form (Fig. 1a). However, capsids with larger diameters were also observed (roughly 3 to 5%). Analyzing 7,823 capsid images from 16 micrographs, we were able to obtain three classes of various sizes from 600 Å to 626 Å (Fig. 2), presumably corresponding to the final stages in the maturation of HPV. Although a subpopulation of even larger capsid species was visible in some images, iterative refinement of all images against four size classes of images resulted in two of the classes merging, yielding only 3 classes (as before). This could be due to the limited number of images in the larger size class, or it might simply indicate that the larger classes are too irregular to be accommodated in an icosahedral model.

Bottom Line: A C175S mutant that cannot achieve normal inter-L1 disulfide cross-links shows maturation-related shrinkage but does not achieve the fully condensed 60-nm form.HPV types associated with a high risk of cancer, such as HPV16, are generally transmitted via sexual contact.The availability of a pseudoatomic model of the fully mature HPV16 virion should help guide understanding of antibody responses elicited by HPV capsid-based vaccines.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Structural Biology, National Institute for Arthritis, Musculoskeletal and Skin Diseases, National Institutes of Health (NIH), Bethesda, Maryland, USA.

Show MeSH
Related in: MedlinePlus