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Crystal Structure of a Retroviral Polyprotein: Prototype Foamy Virus Protease-Reverse Transcriptase (PR-RT)
In most cases, proteolytic processing of the retroviral Pol portion of the Gag-Pol polyprotein precursor produces protease (PR), reverse transcriptase (RT), and integrase (IN). However, foamy viruses (FVs) express Pol separately from Gag and, when Pol is processed, only the IN domain is released. He...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8402755/ https://www.ncbi.nlm.nih.gov/pubmed/34452360 http://dx.doi.org/10.3390/v13081495 |
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author | Harrison, Jerry Joe E. K. Tuske, Steve Das, Kalyan Ruiz, Francesc X. Bauman, Joseph D. Boyer, Paul L. DeStefano, Jeffrey J. Hughes, Stephen H. Arnold, Eddy |
author_facet | Harrison, Jerry Joe E. K. Tuske, Steve Das, Kalyan Ruiz, Francesc X. Bauman, Joseph D. Boyer, Paul L. DeStefano, Jeffrey J. Hughes, Stephen H. Arnold, Eddy |
author_sort | Harrison, Jerry Joe E. K. |
collection | PubMed |
description | In most cases, proteolytic processing of the retroviral Pol portion of the Gag-Pol polyprotein precursor produces protease (PR), reverse transcriptase (RT), and integrase (IN). However, foamy viruses (FVs) express Pol separately from Gag and, when Pol is processed, only the IN domain is released. Here, we report a 2.9 Å resolution crystal structure of the mature PR-RT from prototype FV (PFV) that can carry out both proteolytic processing and reverse transcription but is in a configuration not competent for proteolytic or polymerase activity. PFV PR-RT is monomeric and the architecture of PFV PR is similar to one of the subunits of HIV-1 PR, which is a dimer. There is a C-terminal extension of PFV PR (101-145) that consists of two helices which are adjacent to the base of the RT palm subdomain, and anchors PR to RT. The polymerase domain of PFV RT consists of fingers, palm, thumb, and connection subdomains whose spatial arrangements are similar to the p51 subunit of HIV-1 RT. The RNase H and polymerase domains of PFV RT are connected by flexible linkers. Significant spatial and conformational (sub)domain rearrangements are therefore required for nucleic acid binding. The structure of PFV PR-RT provides insights into the conformational maturation of retroviral Pol polyproteins. |
format | Online Article Text |
id | pubmed-8402755 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-84027552021-08-29 Crystal Structure of a Retroviral Polyprotein: Prototype Foamy Virus Protease-Reverse Transcriptase (PR-RT) Harrison, Jerry Joe E. K. Tuske, Steve Das, Kalyan Ruiz, Francesc X. Bauman, Joseph D. Boyer, Paul L. DeStefano, Jeffrey J. Hughes, Stephen H. Arnold, Eddy Viruses Article In most cases, proteolytic processing of the retroviral Pol portion of the Gag-Pol polyprotein precursor produces protease (PR), reverse transcriptase (RT), and integrase (IN). However, foamy viruses (FVs) express Pol separately from Gag and, when Pol is processed, only the IN domain is released. Here, we report a 2.9 Å resolution crystal structure of the mature PR-RT from prototype FV (PFV) that can carry out both proteolytic processing and reverse transcription but is in a configuration not competent for proteolytic or polymerase activity. PFV PR-RT is monomeric and the architecture of PFV PR is similar to one of the subunits of HIV-1 PR, which is a dimer. There is a C-terminal extension of PFV PR (101-145) that consists of two helices which are adjacent to the base of the RT palm subdomain, and anchors PR to RT. The polymerase domain of PFV RT consists of fingers, palm, thumb, and connection subdomains whose spatial arrangements are similar to the p51 subunit of HIV-1 RT. The RNase H and polymerase domains of PFV RT are connected by flexible linkers. Significant spatial and conformational (sub)domain rearrangements are therefore required for nucleic acid binding. The structure of PFV PR-RT provides insights into the conformational maturation of retroviral Pol polyproteins. MDPI 2021-07-29 /pmc/articles/PMC8402755/ /pubmed/34452360 http://dx.doi.org/10.3390/v13081495 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Harrison, Jerry Joe E. K. Tuske, Steve Das, Kalyan Ruiz, Francesc X. Bauman, Joseph D. Boyer, Paul L. DeStefano, Jeffrey J. Hughes, Stephen H. Arnold, Eddy Crystal Structure of a Retroviral Polyprotein: Prototype Foamy Virus Protease-Reverse Transcriptase (PR-RT) |
title | Crystal Structure of a Retroviral Polyprotein: Prototype Foamy Virus Protease-Reverse Transcriptase (PR-RT) |
title_full | Crystal Structure of a Retroviral Polyprotein: Prototype Foamy Virus Protease-Reverse Transcriptase (PR-RT) |
title_fullStr | Crystal Structure of a Retroviral Polyprotein: Prototype Foamy Virus Protease-Reverse Transcriptase (PR-RT) |
title_full_unstemmed | Crystal Structure of a Retroviral Polyprotein: Prototype Foamy Virus Protease-Reverse Transcriptase (PR-RT) |
title_short | Crystal Structure of a Retroviral Polyprotein: Prototype Foamy Virus Protease-Reverse Transcriptase (PR-RT) |
title_sort | crystal structure of a retroviral polyprotein: prototype foamy virus protease-reverse transcriptase (pr-rt) |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8402755/ https://www.ncbi.nlm.nih.gov/pubmed/34452360 http://dx.doi.org/10.3390/v13081495 |
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