Binding of a Pocket Factor to Hepatitis B Virus Capsids Changes the Rotamer Conformation of Phenylalanine 97

(1) Background: During maturation of the Hepatitis B virus, a viral polymerase inside the capsid transcribes a pre-genomic RNA into a partly double stranded DNA-genome. This is followed by envelopment with surface proteins inserted into a membrane. Envelopment is hypothetically regulated by a struct...

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Autores principales:	Cihan Makbul, Christian Kraft, Matthias Grießmann, Tim Rasmussen, Kilian Katzenberger, Melina Lappe, Paul Pfarr, Cato Stoffer, Mara Stöhr, Anna-Maria Wandinger, Bettina Böttcher
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	Hepatitis B Virus pocket factor Triton X 100 envelopment maturation signal single strand blocking Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/3f40acbcdb1e4470946efea5c6fd5124
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spelling	oai:doaj.org-article:3f40acbcdb1e4470946efea5c6fd51242021-11-25T19:12:22ZBinding of a Pocket Factor to Hepatitis B Virus Capsids Changes the Rotamer Conformation of Phenylalanine 9710.3390/v131121151999-4915https://doaj.org/article/3f40acbcdb1e4470946efea5c6fd51242021-10-01T00:00:00Zhttps://www.mdpi.com/1999-4915/13/11/2115https://doaj.org/toc/1999-4915(1) Background: During maturation of the Hepatitis B virus, a viral polymerase inside the capsid transcribes a pre-genomic RNA into a partly double stranded DNA-genome. This is followed by envelopment with surface proteins inserted into a membrane. Envelopment is hypothetically regulated by a structural signal that reports the maturation state of the genome. NMR data suggest that such a signal can be mimicked by the binding of the detergent Triton X 100 to hydrophobic pockets in the capsid spikes. (2) Methods: We have used electron cryo-microscopy and image processing to elucidate the structural changes that are concomitant with the binding of Triton X 100. (3) Results: Our maps show that Triton X 100 binds with its hydrophobic head group inside the pocket. The hydrophilic tail delineates the outside of the spike and is coordinated via Lys-96. The binding of Triton X 100 changes the rotamer conformation of Phe-97 in helix 4, which enables a π-stacking interaction with Trp-62 in helix 3. Similar changes occur in mutants with low secretion phenotypes (P5T and L60V) and in a mutant with a pre-mature secretion phenotype (F97L). (4) Conclusion: Binding of Triton X 100 is unlikely to mimic structural maturation because mutants with different secretion phenotypes show similar structural responses.Cihan MakbulChristian KraftMatthias GrießmannTim RasmussenKilian KatzenbergerMelina LappePaul PfarrCato StofferMara StöhrAnna-Maria WandingerBettina BöttcherMDPI AGarticleHepatitis B Viruspocket factorTriton X 100envelopmentmaturation signalsingle strand blockingMicrobiologyQR1-502ENViruses, Vol 13, Iss 2115, p 2115 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Hepatitis B Virus pocket factor Triton X 100 envelopment maturation signal single strand blocking Microbiology QR1-502
spellingShingle	Hepatitis B Virus pocket factor Triton X 100 envelopment maturation signal single strand blocking Microbiology QR1-502 Cihan Makbul Christian Kraft Matthias Grießmann Tim Rasmussen Kilian Katzenberger Melina Lappe Paul Pfarr Cato Stoffer Mara Stöhr Anna-Maria Wandinger Bettina Böttcher Binding of a Pocket Factor to Hepatitis B Virus Capsids Changes the Rotamer Conformation of Phenylalanine 97
description	(1) Background: During maturation of the Hepatitis B virus, a viral polymerase inside the capsid transcribes a pre-genomic RNA into a partly double stranded DNA-genome. This is followed by envelopment with surface proteins inserted into a membrane. Envelopment is hypothetically regulated by a structural signal that reports the maturation state of the genome. NMR data suggest that such a signal can be mimicked by the binding of the detergent Triton X 100 to hydrophobic pockets in the capsid spikes. (2) Methods: We have used electron cryo-microscopy and image processing to elucidate the structural changes that are concomitant with the binding of Triton X 100. (3) Results: Our maps show that Triton X 100 binds with its hydrophobic head group inside the pocket. The hydrophilic tail delineates the outside of the spike and is coordinated via Lys-96. The binding of Triton X 100 changes the rotamer conformation of Phe-97 in helix 4, which enables a π-stacking interaction with Trp-62 in helix 3. Similar changes occur in mutants with low secretion phenotypes (P5T and L60V) and in a mutant with a pre-mature secretion phenotype (F97L). (4) Conclusion: Binding of Triton X 100 is unlikely to mimic structural maturation because mutants with different secretion phenotypes show similar structural responses.
format	article
author	Cihan Makbul Christian Kraft Matthias Grießmann Tim Rasmussen Kilian Katzenberger Melina Lappe Paul Pfarr Cato Stoffer Mara Stöhr Anna-Maria Wandinger Bettina Böttcher
author_facet	Cihan Makbul Christian Kraft Matthias Grießmann Tim Rasmussen Kilian Katzenberger Melina Lappe Paul Pfarr Cato Stoffer Mara Stöhr Anna-Maria Wandinger Bettina Böttcher
author_sort	Cihan Makbul
title	Binding of a Pocket Factor to Hepatitis B Virus Capsids Changes the Rotamer Conformation of Phenylalanine 97
title_short	Binding of a Pocket Factor to Hepatitis B Virus Capsids Changes the Rotamer Conformation of Phenylalanine 97
title_full	Binding of a Pocket Factor to Hepatitis B Virus Capsids Changes the Rotamer Conformation of Phenylalanine 97
title_fullStr	Binding of a Pocket Factor to Hepatitis B Virus Capsids Changes the Rotamer Conformation of Phenylalanine 97
title_full_unstemmed	Binding of a Pocket Factor to Hepatitis B Virus Capsids Changes the Rotamer Conformation of Phenylalanine 97
title_sort	binding of a pocket factor to hepatitis b virus capsids changes the rotamer conformation of phenylalanine 97
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/3f40acbcdb1e4470946efea5c6fd5124
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Binding of a Pocket Factor to Hepatitis B Virus Capsids Changes the Rotamer Conformation of Phenylalanine 97

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