High resolution cryo EM analysis of HPV16 identifies minor structural protein L2 and describes capsid flexibility

Abstract Human papillomavirus (HPV) is a significant health burden and leading cause of virus-induced cancers. HPV is epitheliotropic and its replication is tightly associated with terminal keratinocyte differentiation making production and purification of high titer virus preparations for research...

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Autores principales:	Daniel J. Goetschius, Samantha R. Hartmann, Suriyasri Subramanian, Carol M. Bator, Neil D. Christensen, Susan L. Hafenstein
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/e04b64485e644667b0e59a3751e54ebe
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spelling	oai:doaj.org-article:e04b64485e644667b0e59a3751e54ebe2021-12-02T12:15:01ZHigh resolution cryo EM analysis of HPV16 identifies minor structural protein L2 and describes capsid flexibility10.1038/s41598-021-83076-52045-2322https://doaj.org/article/e04b64485e644667b0e59a3751e54ebe2021-02-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-83076-5https://doaj.org/toc/2045-2322Abstract Human papillomavirus (HPV) is a significant health burden and leading cause of virus-induced cancers. HPV is epitheliotropic and its replication is tightly associated with terminal keratinocyte differentiation making production and purification of high titer virus preparations for research problematic, therefore alternative HPV production methods have been developed for virological and structural studies. In this study we use HPV16 quasivirus, composed of HPV16 L1/L2 capsid proteins with a packaged cottontail rabbit papillomavirus genome. We have achieved the first high resolution, 3.1 Å, structure of HPV16 by using a local subvolume refinement approach. The high resolution enabled us to build L1 unambiguously and identify L2 protein strands. The L2 density is incorporated adjacent to conserved L1 residues on the interior of the capsid. Further interpretation with our own software for Icosahedral Subvolume Extraction and Correlated Classification revealed flexibility, on the whole-particle level through diameter analysis and local movement with inter-capsomer analysis. Inter-capsomer expansion or contraction, governed by the connecting arms, showed no bias in the magnitude or direction of capsomer movement. We propose that papillomavirus capsids are dynamic and capsomers move as rigid bodies connected by flexible linkers. The resulting virus structure will provide a framework for continuing biochemical, genetic and biophysical research for papillomaviruses. Furthermore, our approach has allowed insight into the resolution barrier that has previously been a limitation in papillomavirus structural studies.Daniel J. GoetschiusSamantha R. HartmannSuriyasri SubramanianCarol M. BatorNeil D. ChristensenSusan L. HafensteinNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-15 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Daniel J. Goetschius Samantha R. Hartmann Suriyasri Subramanian Carol M. Bator Neil D. Christensen Susan L. Hafenstein High resolution cryo EM analysis of HPV16 identifies minor structural protein L2 and describes capsid flexibility
description	Abstract Human papillomavirus (HPV) is a significant health burden and leading cause of virus-induced cancers. HPV is epitheliotropic and its replication is tightly associated with terminal keratinocyte differentiation making production and purification of high titer virus preparations for research problematic, therefore alternative HPV production methods have been developed for virological and structural studies. In this study we use HPV16 quasivirus, composed of HPV16 L1/L2 capsid proteins with a packaged cottontail rabbit papillomavirus genome. We have achieved the first high resolution, 3.1 Å, structure of HPV16 by using a local subvolume refinement approach. The high resolution enabled us to build L1 unambiguously and identify L2 protein strands. The L2 density is incorporated adjacent to conserved L1 residues on the interior of the capsid. Further interpretation with our own software for Icosahedral Subvolume Extraction and Correlated Classification revealed flexibility, on the whole-particle level through diameter analysis and local movement with inter-capsomer analysis. Inter-capsomer expansion or contraction, governed by the connecting arms, showed no bias in the magnitude or direction of capsomer movement. We propose that papillomavirus capsids are dynamic and capsomers move as rigid bodies connected by flexible linkers. The resulting virus structure will provide a framework for continuing biochemical, genetic and biophysical research for papillomaviruses. Furthermore, our approach has allowed insight into the resolution barrier that has previously been a limitation in papillomavirus structural studies.
format	article
author	Daniel J. Goetschius Samantha R. Hartmann Suriyasri Subramanian Carol M. Bator Neil D. Christensen Susan L. Hafenstein
author_facet	Daniel J. Goetschius Samantha R. Hartmann Suriyasri Subramanian Carol M. Bator Neil D. Christensen Susan L. Hafenstein
author_sort	Daniel J. Goetschius
title	High resolution cryo EM analysis of HPV16 identifies minor structural protein L2 and describes capsid flexibility
title_short	High resolution cryo EM analysis of HPV16 identifies minor structural protein L2 and describes capsid flexibility
title_full	High resolution cryo EM analysis of HPV16 identifies minor structural protein L2 and describes capsid flexibility
title_fullStr	High resolution cryo EM analysis of HPV16 identifies minor structural protein L2 and describes capsid flexibility
title_full_unstemmed	High resolution cryo EM analysis of HPV16 identifies minor structural protein L2 and describes capsid flexibility
title_sort	high resolution cryo em analysis of hpv16 identifies minor structural protein l2 and describes capsid flexibility
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/e04b64485e644667b0e59a3751e54ebe
work_keys_str_mv	AT danieljgoetschius highresolutioncryoemanalysisofhpv16identifiesminorstructuralproteinl2anddescribescapsidflexibility AT samantharhartmann highresolutioncryoemanalysisofhpv16identifiesminorstructuralproteinl2anddescribescapsidflexibility AT suriyasrisubramanian highresolutioncryoemanalysisofhpv16identifiesminorstructuralproteinl2anddescribescapsidflexibility AT carolmbator highresolutioncryoemanalysisofhpv16identifiesminorstructuralproteinl2anddescribescapsidflexibility AT neildchristensen highresolutioncryoemanalysisofhpv16identifiesminorstructuralproteinl2anddescribescapsidflexibility AT susanlhafenstein highresolutioncryoemanalysisofhpv16identifiesminorstructuralproteinl2anddescribescapsidflexibility
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High resolution cryo EM analysis of HPV16 identifies minor structural protein L2 and describes capsid flexibility

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