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Structural insight into host plasma membrane association and assembly of HIV-1 matrix protein
Oligomerization of Pr55(Gag) is a critical step of the late stage of the HIV life cycle. It has been known that the binding of IP6, an abundant endogenous cyclitol molecule at the MA domain, has been linked to the oligomerization of Pr55(Gag). However, the exact binding site of IP6 on MA remains unk...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8339130/ https://www.ncbi.nlm.nih.gov/pubmed/34349176 http://dx.doi.org/10.1038/s41598-021-95236-8 |
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author | Ciftci, Halilibrahim Tateishi, Hiroshi Koiwai, Kotaro Koga, Ryoko Anraku, Kensaku Monde, Kazuaki Dağ, Çağdaş Destan, Ebru Yuksel, Busra Ayan, Esra Yildirim, Gunseli Yigin, Merve Ertem, F. Betul Shafiei, Alaleh Guven, Omur Besler, Sabri O. Sierra, Raymond G. Yoon, Chun Hong Su, Zhen Liang, Mengling Acar, Burcin Haliloglu, Turkan Otsuka, Masami Yumoto, Fumiaki Fujita, Mikako Senda, Toshiya DeMirci, Hasan |
author_facet | Ciftci, Halilibrahim Tateishi, Hiroshi Koiwai, Kotaro Koga, Ryoko Anraku, Kensaku Monde, Kazuaki Dağ, Çağdaş Destan, Ebru Yuksel, Busra Ayan, Esra Yildirim, Gunseli Yigin, Merve Ertem, F. Betul Shafiei, Alaleh Guven, Omur Besler, Sabri O. Sierra, Raymond G. Yoon, Chun Hong Su, Zhen Liang, Mengling Acar, Burcin Haliloglu, Turkan Otsuka, Masami Yumoto, Fumiaki Fujita, Mikako Senda, Toshiya DeMirci, Hasan |
author_sort | Ciftci, Halilibrahim |
collection | PubMed |
description | Oligomerization of Pr55(Gag) is a critical step of the late stage of the HIV life cycle. It has been known that the binding of IP6, an abundant endogenous cyclitol molecule at the MA domain, has been linked to the oligomerization of Pr55(Gag). However, the exact binding site of IP6 on MA remains unknown and the structural details of this interaction are missing. Here, we present three high-resolution crystal structures of the MA domain in complex with IP6 molecules to reveal its binding mode. Additionally, extensive Differential Scanning Fluorimetry analysis combined with cryo- and ambient-temperature X-ray crystallography and GNM-based transfer entropy calculations identify the key residues that participate in IP6 binding. Our data provide novel insights about the multilayered HIV-1 virion assembly process that involves the interplay of IP6 with PIP2, a phosphoinositide essential for the binding of Pr55(Gag) to membrane. IP6 and PIP2 have neighboring alternate binding sites within the same highly basic region (residues 18–33). This indicates that IP6 and PIP2 bindings are not mutually exclusive and may play a key role in coordinating virion particles’ membrane localization. Based on our three different IP6-MA complex crystal structures, we propose a new model that involves IP6 coordination of the oligomerization of outer MA and inner CA domain’s 2D layers during assembly and budding. |
format | Online Article Text |
id | pubmed-8339130 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-83391302021-08-06 Structural insight into host plasma membrane association and assembly of HIV-1 matrix protein Ciftci, Halilibrahim Tateishi, Hiroshi Koiwai, Kotaro Koga, Ryoko Anraku, Kensaku Monde, Kazuaki Dağ, Çağdaş Destan, Ebru Yuksel, Busra Ayan, Esra Yildirim, Gunseli Yigin, Merve Ertem, F. Betul Shafiei, Alaleh Guven, Omur Besler, Sabri O. Sierra, Raymond G. Yoon, Chun Hong Su, Zhen Liang, Mengling Acar, Burcin Haliloglu, Turkan Otsuka, Masami Yumoto, Fumiaki Fujita, Mikako Senda, Toshiya DeMirci, Hasan Sci Rep Article Oligomerization of Pr55(Gag) is a critical step of the late stage of the HIV life cycle. It has been known that the binding of IP6, an abundant endogenous cyclitol molecule at the MA domain, has been linked to the oligomerization of Pr55(Gag). However, the exact binding site of IP6 on MA remains unknown and the structural details of this interaction are missing. Here, we present three high-resolution crystal structures of the MA domain in complex with IP6 molecules to reveal its binding mode. Additionally, extensive Differential Scanning Fluorimetry analysis combined with cryo- and ambient-temperature X-ray crystallography and GNM-based transfer entropy calculations identify the key residues that participate in IP6 binding. Our data provide novel insights about the multilayered HIV-1 virion assembly process that involves the interplay of IP6 with PIP2, a phosphoinositide essential for the binding of Pr55(Gag) to membrane. IP6 and PIP2 have neighboring alternate binding sites within the same highly basic region (residues 18–33). This indicates that IP6 and PIP2 bindings are not mutually exclusive and may play a key role in coordinating virion particles’ membrane localization. Based on our three different IP6-MA complex crystal structures, we propose a new model that involves IP6 coordination of the oligomerization of outer MA and inner CA domain’s 2D layers during assembly and budding. Nature Publishing Group UK 2021-08-04 /pmc/articles/PMC8339130/ /pubmed/34349176 http://dx.doi.org/10.1038/s41598-021-95236-8 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Ciftci, Halilibrahim Tateishi, Hiroshi Koiwai, Kotaro Koga, Ryoko Anraku, Kensaku Monde, Kazuaki Dağ, Çağdaş Destan, Ebru Yuksel, Busra Ayan, Esra Yildirim, Gunseli Yigin, Merve Ertem, F. Betul Shafiei, Alaleh Guven, Omur Besler, Sabri O. Sierra, Raymond G. Yoon, Chun Hong Su, Zhen Liang, Mengling Acar, Burcin Haliloglu, Turkan Otsuka, Masami Yumoto, Fumiaki Fujita, Mikako Senda, Toshiya DeMirci, Hasan Structural insight into host plasma membrane association and assembly of HIV-1 matrix protein |
title | Structural insight into host plasma membrane association and assembly of HIV-1 matrix protein |
title_full | Structural insight into host plasma membrane association and assembly of HIV-1 matrix protein |
title_fullStr | Structural insight into host plasma membrane association and assembly of HIV-1 matrix protein |
title_full_unstemmed | Structural insight into host plasma membrane association and assembly of HIV-1 matrix protein |
title_short | Structural insight into host plasma membrane association and assembly of HIV-1 matrix protein |
title_sort | structural insight into host plasma membrane association and assembly of hiv-1 matrix protein |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8339130/ https://www.ncbi.nlm.nih.gov/pubmed/34349176 http://dx.doi.org/10.1038/s41598-021-95236-8 |
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