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...
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Nature Portfolio
2021
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oai:doaj.org-article:77d919cd60ce407e9fad3b1b4378ff452021-12-02T14:53:34ZStructural insight into host plasma membrane association and assembly of HIV-1 matrix protein10.1038/s41598-021-95236-82045-2322https://doaj.org/article/77d919cd60ce407e9fad3b1b4378ff452021-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-95236-8https://doaj.org/toc/2045-2322Abstract 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.Halilibrahim CiftciHiroshi TateishiKotaro KoiwaiRyoko KogaKensaku AnrakuKazuaki MondeÇağdaş DağEbru DestanBusra YukselEsra AyanGunseli YildirimMerve YiginF. Betul ErtemAlaleh ShafieiOmur GuvenSabri O. BeslerRaymond G. SierraChun Hong YoonZhen SuMengling LiangBurcin AcarTurkan HalilogluMasami OtsukaFumiaki YumotoMikako FujitaToshiya SendaHasan DeMirciNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-14 (2021) |
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DOAJ |
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Medicine R Science Q 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 |
| 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. |
| format |
article |
| 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 |
| title |
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_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_sort |
structural insight into host plasma membrane association and assembly of hiv-1 matrix protein |
| publisher |
Nature Portfolio |
| publishDate |
2021 |
| url |
https://doaj.org/article/77d919cd60ce407e9fad3b1b4378ff45 |
| work_keys_str_mv |
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