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Structural insight into host plasma membrane association and assembly of HIV-1 matrix protein

By 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 Demirci1

1. Biosciences Division at SLAC National Accelerator Laboratory

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Category

BioXFEL Publications

Published on

Type

journal-article

Author

Halilibrahim Ciftci and Hiroshi Tateishi and Kotaro Koiwai and Ryoko Koga and Kensaku Anraku and Kazuaki Monde and Çağdaş Dağ and Ebru Destan and Busra Yuksel and Esra Ayan and Gunseli Yildirim and Merve Yigin and F. Betul Ertem and Alaleh Shafiei and Omur Guven and Sabri O. Besler and Raymond G. Sierra and Chun Hong Yoon and Zhen Su and Mengling Liang and Burcin Acar and Turkan Haliloglu and Masami Otsuka and Fumiaki Yumoto and Mikako Fujita and Toshiya Senda and Hasan DeMirci

Citation

Ciftci, H. et al., 2021. Structural insight into host plasma membrane association and assembly of HIV-1 matrix protein. Scientific Reports, 11(1). Available at: http://dx.doi.org/10.1038/s41598-021-95236-8.

Abstract

AbstractOligomerization 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.

DOI

http://dx.doi.org/10.1038/s41598-021-95236-8

Funding

NSF-STC Biology with X-ray Lasers (NSF-1231306)