6BHT

HIV-1 CA hexamer in complex with IP6, orthorhombic crystal form

6BHT の概要

• エントリーDOI: 10.2210/pdb6bht/pdb
• 関連するPDBエントリー: 6BHR 6BHS
• 分子名称: Capsid protein p24, INOSITOL HEXAKISPHOSPHATE (3 entities in total)
• 機能のキーワード: assembly, co-factor, viral protein
• 由来する生物種: Human immunodeficiency virus type 1 (NEW YORK-5 ISOLATE)
• タンパク質・核酸の鎖数: 12
• 化学式量合計: 308175.39

構造登録者

Zadrozny, K.,Wagner, J.M.,Ganser-Pornillos, B.K.,Pornillos, O. (登録日: 2017-10-31, 公開日: 2018-08-01, 最終更新日: 2023-10-04)

主引用文献

Dick, R.A.,Zadrozny, K.K.,Xu, C.,Schur, F.K.M.,Lyddon, T.D.,Ricana, C.L.,Wagner, J.M.,Perilla, J.R.,Ganser-Pornillos, B.K.,Johnson, M.C.,Pornillos, O.,Vogt, V.M.
Inositol phosphates are assembly co-factors for HIV-1.
Nature, 560:509-512, 2018

PubMed Abstract: A short, 14-amino-acid segment called SP1, located in the Gag structural protein, 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 membrane. 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 inhibitors. Here, using a combination of structural and functional analyses, we show that inositol hexakisphosphate (InsP6, also known as IP) facilitates the formation of the six-helix bundle and assembly of the immature HIV-1 Gag lattice. IP 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 IP interaction promotes the assembly of the mature capsid lattice. These studies identify IP as a naturally occurring small molecule that promotes both assembly and maturation of HIV-1.

PubMed: 30069050
DOI: 10.1038/s41586-018-0396-4

実験手法

X-RAY DIFFRACTION (2.689 Å)