Construction of atomic models of full hepatitis B vaccine particles at different stages of maturation.

Autor: Berthier L; PRABI-LG - Laboratoire de Biologie Tissulaire et d'ingénierie Thérapeutique (LBTI), UMR, UCBL, CNRS 5305, Université de Lyon, 7 Passage du Vercors, 69367, Lyon Cedex 07, France., Brass O; Sanofi Pasteur, avenue Ch. Mérieux, F-69280, Marcy-l'Etoile, France., Deleage G; PRABI-LG - Laboratoire de Biologie Tissulaire et d'ingénierie Thérapeutique (LBTI), UMR, UCBL, CNRS 5305, Université de Lyon, 7 Passage du Vercors, 69367, Lyon Cedex 07, France., Terreux R; PRABI-LG - Laboratoire de Biologie Tissulaire et d'ingénierie Thérapeutique (LBTI), UMR, UCBL, CNRS 5305, Université de Lyon, 7 Passage du Vercors, 69367, Lyon Cedex 07, France. Electronic address: raphael.terreux@ibcp.fr.
Jazyk: angličtina
Zdroj: Journal of molecular graphics & modelling [J Mol Graph Model] 2020 Jul; Vol. 98, pp. 107610. Date of Electronic Publication: 2020 Apr 09.
DOI: 10.1016/j.jmgm.2020.107610
Abstrakt: Hepatitis B, one of the world's most common liver infections, is caused by the Hepatitis B Virus (HBV). Via the infected cells, this virus generates non pathogen particles with similar surface structures as those found in the full virus. These particles are used in a recombinant form (HBsAg) to produce efficient vaccines. The atomic structure of the HBsAg particles is currently unsolved, and the only existing structural data for the full particle were obtained by electronic microscopy with a maximum resolution of 12 Å. As many vaccines, HBsAg is a complex bio-system. This complexity results from numerous sources of heterogeneity, and traditional bio-immuno-chemistry analytic tools are often limited in their ability to fully describe the molecular surface or the particle. For the Hepatitis B vaccine particle (HBsAg), no atomic data are available so far. In this study, we used the principal well-known elements of HBsAg structure to reconstitute and model the full HBsAg particle assembly at a molecular level (protein assembly, particle formation and maturation). Full HBsAg particle atomic models were built based on an exhaustive experimental data review, amino acid sequence analysis, iterative threading modeling, and molecular dynamic approaches.
(Copyright © 2020 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE