Cargando…

Subassemblies and Asymmetry in Assembly of Herpes Simplex Virus Procapsid

The herpes simplex virus 1 (HSV-1) capsid is a massive particle (~200 MDa; 1,250-Å diameter) with T=16 icosahedral symmetry. It initially assembles as a procapsid with ~4,000 protein subunits of 11 different kinds. The procapsid undergoes major changes in structure and composition as it matures, a p...

Descripción completa

Detalles Bibliográficos
Autores principales: Aksyuk, Anastasia A., Newcomb, William W., Cheng, Naiqian, Winkler, Dennis C., Fontana, Juan, Heymann, J. Bernard, Steven, Alasdair C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society of Microbiology 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4611051/
https://www.ncbi.nlm.nih.gov/pubmed/26443463
http://dx.doi.org/10.1128/mBio.01525-15
_version_ 1782396041416409088
author Aksyuk, Anastasia A.
Newcomb, William W.
Cheng, Naiqian
Winkler, Dennis C.
Fontana, Juan
Heymann, J. Bernard
Steven, Alasdair C.
author_facet Aksyuk, Anastasia A.
Newcomb, William W.
Cheng, Naiqian
Winkler, Dennis C.
Fontana, Juan
Heymann, J. Bernard
Steven, Alasdair C.
author_sort Aksyuk, Anastasia A.
collection PubMed
description The herpes simplex virus 1 (HSV-1) capsid is a massive particle (~200 MDa; 1,250-Å diameter) with T=16 icosahedral symmetry. It initially assembles as a procapsid with ~4,000 protein subunits of 11 different kinds. The procapsid undergoes major changes in structure and composition as it matures, a process driven by proteolysis and expulsion of the internal scaffolding protein. Assembly also relies on an external scaffolding protein, the triplex, an α(2)β heterotrimer that coordinates neighboring capsomers in the procapsid and becomes a stabilizing clamp in the mature capsid. To investigate the mechanisms that regulate its assembly, we developed a novel isolation procedure for the metastable procapsid and collected a large set of cryo-electron microscopy data. In addition to procapsids, these preparations contain maturation intermediates, which were distinguished by classifying the images and calculating a three-dimensional reconstruction for each class. Appraisal of the procapsid structure led to a new model for assembly; in it, the protomer (assembly unit) consists of one triplex, surrounded by three major capsid protein (MCP) subunits. The model exploits the triplexes’ departure from 3-fold symmetry to explain the highly skewed MCP hexamers, the triplex orientations at each 3-fold site, and the T=16 architecture. These observations also yielded new insights into maturation.
format Online
Article
Text
id pubmed-4611051
institution National Center for Biotechnology Information
language English
publishDate 2015
publisher American Society of Microbiology
record_format MEDLINE/PubMed
spelling pubmed-46110512015-10-25 Subassemblies and Asymmetry in Assembly of Herpes Simplex Virus Procapsid Aksyuk, Anastasia A. Newcomb, William W. Cheng, Naiqian Winkler, Dennis C. Fontana, Juan Heymann, J. Bernard Steven, Alasdair C. mBio Research Article The herpes simplex virus 1 (HSV-1) capsid is a massive particle (~200 MDa; 1,250-Å diameter) with T=16 icosahedral symmetry. It initially assembles as a procapsid with ~4,000 protein subunits of 11 different kinds. The procapsid undergoes major changes in structure and composition as it matures, a process driven by proteolysis and expulsion of the internal scaffolding protein. Assembly also relies on an external scaffolding protein, the triplex, an α(2)β heterotrimer that coordinates neighboring capsomers in the procapsid and becomes a stabilizing clamp in the mature capsid. To investigate the mechanisms that regulate its assembly, we developed a novel isolation procedure for the metastable procapsid and collected a large set of cryo-electron microscopy data. In addition to procapsids, these preparations contain maturation intermediates, which were distinguished by classifying the images and calculating a three-dimensional reconstruction for each class. Appraisal of the procapsid structure led to a new model for assembly; in it, the protomer (assembly unit) consists of one triplex, surrounded by three major capsid protein (MCP) subunits. The model exploits the triplexes’ departure from 3-fold symmetry to explain the highly skewed MCP hexamers, the triplex orientations at each 3-fold site, and the T=16 architecture. These observations also yielded new insights into maturation. American Society of Microbiology 2015-10-06 /pmc/articles/PMC4611051/ /pubmed/26443463 http://dx.doi.org/10.1128/mBio.01525-15 Text en Copyright © 2015, Aksyuk et al. http://creativecommons.org/licenses/by-nc-sa/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution-Noncommercial-ShareAlike 3.0 Unported license (http://creativecommons.org/licenses/by-nc-sa/3.0/) , which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Aksyuk, Anastasia A.
Newcomb, William W.
Cheng, Naiqian
Winkler, Dennis C.
Fontana, Juan
Heymann, J. Bernard
Steven, Alasdair C.
Subassemblies and Asymmetry in Assembly of Herpes Simplex Virus Procapsid
title Subassemblies and Asymmetry in Assembly of Herpes Simplex Virus Procapsid
title_full Subassemblies and Asymmetry in Assembly of Herpes Simplex Virus Procapsid
title_fullStr Subassemblies and Asymmetry in Assembly of Herpes Simplex Virus Procapsid
title_full_unstemmed Subassemblies and Asymmetry in Assembly of Herpes Simplex Virus Procapsid
title_short Subassemblies and Asymmetry in Assembly of Herpes Simplex Virus Procapsid
title_sort subassemblies and asymmetry in assembly of herpes simplex virus procapsid
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4611051/
https://www.ncbi.nlm.nih.gov/pubmed/26443463
http://dx.doi.org/10.1128/mBio.01525-15
work_keys_str_mv AT aksyukanastasiaa subassembliesandasymmetryinassemblyofherpessimplexvirusprocapsid
AT newcombwilliamw subassembliesandasymmetryinassemblyofherpessimplexvirusprocapsid
AT chengnaiqian subassembliesandasymmetryinassemblyofherpessimplexvirusprocapsid
AT winklerdennisc subassembliesandasymmetryinassemblyofherpessimplexvirusprocapsid
AT fontanajuan subassembliesandasymmetryinassemblyofherpessimplexvirusprocapsid
AT heymannjbernard subassembliesandasymmetryinassemblyofherpessimplexvirusprocapsid
AT stevenalasdairc subassembliesandasymmetryinassemblyofherpessimplexvirusprocapsid