Inositol phosphates are assembly co-factors for HIV-1

Robert A. Dick (), Kaneil K. Zadrozny, Chaoyi Xu, Florian K. M. Schur, Terri D. Lyddon, Clifton L. Ricana, Jonathan M. Wagner, Juan R. Perilla, Barbie K. Ganser-Pornillos, Marc C. Johnson, Owen Pornillos () and Volker M. Vogt
Additional contact information
Robert A. Dick: Cornell University
Kaneil K. Zadrozny: University of Virginia
Chaoyi Xu: University of Delaware
Florian K. M. Schur: Structural and Computational Biology Unit, EMBL
Terri D. Lyddon: University of Missouri
Clifton L. Ricana: University of Missouri
Jonathan M. Wagner: University of Virginia
Juan R. Perilla: University of Delaware
Barbie K. Ganser-Pornillos: University of Virginia
Marc C. Johnson: University of Missouri
Owen Pornillos: University of Virginia
Volker M. Vogt: Cornell University

Nature, 2018, vol. 560, issue 7719, 509-512

Abstract: Abstract A short, 14-amino-acid segment called SP1, located in the Gag structural protein1, has a critical role during the formation of the HIV-1 virus particle. During virus assembly, the SP1 peptide and seven preceding residues fold into a six-helix bundle, which holds together the Gag hexamer and facilitates the formation of a curved immature hexagonal lattice underneath the viral membrane2,3. Upon completion of assembly and budding, proteolytic cleavage of Gag leads to virus maturation, in which the immature lattice is broken down; the liberated CA domain of Gag then re-assembles into the mature conical capsid that encloses the viral genome and associated enzymes. Folding and proteolysis of the six-helix bundle are crucial rate-limiting steps of both Gag assembly and disassembly, and the six-helix bundle is an established target of HIV-1 inhibitors4,5. Here, using a combination of structural and functional analyses, we show that inositol hexakisphosphate (InsP6, also known as IP6) facilitates the formation of the six-helix bundle and assembly of the immature HIV-1 Gag lattice. IP6 makes ionic contacts with two rings of lysine residues at the centre of the Gag hexamer. Proteolytic cleavage then unmasks an alternative binding site, where IP6 interaction promotes the assembly of the mature capsid lattice. These studies identify IP6 as a naturally occurring small molecule that promotes both assembly and maturation of HIV-1.

Date: 2018
References: Add references at CitEc
Citations: View citations in EconPapers (4)

Downloads: (external link)
https://www.nature.com/articles/s41586-018-0396-4 Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:560:y:2018:i:7719:d:10.1038_s41586-018-0396-4

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/s41586-018-0396-4

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().