Structural insight into host plasma membrane association and assembly of HIV-1 matrix protein
Abstract Oligomerization of Pr55Gag 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 Pr55Gag. However, the exact binding site of IP6 on MA remain...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2021-08-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-021-95236-8 |
| _version_ | 1818421073860886528 |
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| author | Halilibrahim Ciftci Hiroshi Tateishi Kotaro Koiwai Ryoko Koga Kensaku Anraku Kazuaki Monde Çağdaş Dağ Ebru Destan Busra Yuksel Esra Ayan Gunseli Yildirim Merve Yigin F. Betul Ertem Alaleh Shafiei Omur Guven Sabri O. Besler Raymond G. Sierra Chun Hong Yoon Zhen Su Mengling Liang Burcin Acar Turkan Haliloglu Masami Otsuka Fumiaki Yumoto Mikako Fujita Toshiya Senda Hasan DeMirci |
| author_facet | Halilibrahim Ciftci Hiroshi Tateishi Kotaro Koiwai Ryoko Koga Kensaku Anraku Kazuaki Monde Çağdaş Dağ Ebru Destan Busra Yuksel Esra Ayan Gunseli Yildirim Merve Yigin F. Betul Ertem Alaleh Shafiei Omur Guven Sabri O. Besler Raymond G. Sierra Chun Hong Yoon Zhen Su Mengling Liang Burcin Acar Turkan Haliloglu Masami Otsuka Fumiaki Yumoto Mikako Fujita Toshiya Senda Hasan DeMirci |
| author_sort | Halilibrahim Ciftci |
| collection | DOAJ |
| description | Abstract Oligomerization of Pr55Gag 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 Pr55Gag. 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 Pr55Gag 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. |
| first_indexed | 2024-12-14T13:04:34Z |
| format | Article |
| id | doaj.art-77d919cd60ce407e9fad3b1b4378ff45 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-14T13:04:34Z |
| publishDate | 2021-08-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-77d919cd60ce407e9fad3b1b4378ff452022-12-21T23:00:21ZengNature PortfolioScientific Reports2045-23222021-08-0111111410.1038/s41598-021-95236-8Structural insight into host plasma membrane association and assembly of HIV-1 matrix proteinHalilibrahim Ciftci0Hiroshi Tateishi1Kotaro Koiwai2Ryoko Koga3Kensaku Anraku4Kazuaki Monde5Çağdaş Dağ6Ebru Destan7Busra Yuksel8Esra Ayan9Gunseli Yildirim10Merve Yigin11F. Betul Ertem12Alaleh Shafiei13Omur Guven14Sabri O. Besler15Raymond G. Sierra16Chun Hong Yoon17Zhen Su18Mengling Liang19Burcin Acar20Turkan Haliloglu21Masami Otsuka22Fumiaki Yumoto23Mikako Fujita24Toshiya Senda25Hasan DeMirci26Medicinal and Biological Chemistry Science Farm Joint Research Laboratory, Faculty of Life Sciences, Kumamoto UniversityMedicinal and Biological Chemistry Science Farm Joint Research Laboratory, Faculty of Life Sciences, Kumamoto UniversityStructural Biology Research Center, Institute of Materials Structure Science, KEK/High Energy Accelerator Research OrganizationMedicinal and Biological Chemistry Science Farm Joint Research Laboratory, Faculty of Life Sciences, Kumamoto UniversityDepartment of Medical Technology, Kumamoto Health Science UniversityDepartment of Microbiology, Faculty of Life Sciences, Kumamoto UniversityStanford PULSE Institute, SLAC National Accelerator LaboratoryStanford PULSE Institute, SLAC National Accelerator LaboratoryStanford PULSE Institute, SLAC National Accelerator LaboratoryStanford PULSE Institute, SLAC National Accelerator LaboratoryStanford PULSE Institute, SLAC National Accelerator LaboratoryStanford PULSE Institute, SLAC National Accelerator LaboratoryDepartment of Molecular Biology and Genetics, Koc UniversityDepartment of Molecular Biology and Genetics, Koc UniversityDepartment of Molecular Biology and Genetics, Koc UniversityDepartment of Molecular Biology and Genetics, Koc UniversityLinac Coherent Light Source, SLAC National Accelerator LaboratoryLinac Coherent Light Source, SLAC National Accelerator LaboratoryLinac Coherent Light Source, SLAC National Accelerator LaboratoryLinac Coherent Light Source, SLAC National Accelerator LaboratoryPolymer Research Center, Bogazici UniversityDepartment of Chemical Engineering, Bogazici UniversityMedicinal and Biological Chemistry Science Farm Joint Research Laboratory, Faculty of Life Sciences, Kumamoto UniversityStructural Biology Research Center, Institute of Materials Structure Science, KEK/High Energy Accelerator Research OrganizationMedicinal and Biological Chemistry Science Farm Joint Research Laboratory, Faculty of Life Sciences, Kumamoto UniversityStructural Biology Research Center, Institute of Materials Structure Science, KEK/High Energy Accelerator Research OrganizationStanford PULSE Institute, SLAC National Accelerator LaboratoryAbstract Oligomerization of Pr55Gag 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 Pr55Gag. 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 Pr55Gag 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.https://doi.org/10.1038/s41598-021-95236-8 |
| spellingShingle | Halilibrahim Ciftci Hiroshi Tateishi Kotaro Koiwai Ryoko Koga Kensaku Anraku Kazuaki Monde Çağdaş Dağ Ebru Destan Busra Yuksel Esra Ayan Gunseli Yildirim Merve Yigin F. Betul Ertem Alaleh Shafiei Omur Guven Sabri O. Besler Raymond G. Sierra Chun Hong Yoon Zhen Su Mengling Liang Burcin Acar Turkan Haliloglu Masami Otsuka Fumiaki Yumoto Mikako Fujita Toshiya Senda Hasan DeMirci Structural insight into host plasma membrane association and assembly of HIV-1 matrix protein Scientific Reports |
| 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 |
| url | https://doi.org/10.1038/s41598-021-95236-8 |
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