PDBsum entry 6bhs

Viral protein

PDB id: 6bhs

Contents

Protein chain

207 a.a.

Ligands

IHP

Waters ×145

PDB id:

6bhs

Name:

Viral protein

Title:

HIV-1 ca hexamer in complex with ip6, hexagonal crystal form

Structure:

Capsid protein p24. Chain: a. Engineered: yes. Mutation: yes

Source:

Human immunodeficiency virus type 1 group m subtype b (isolate ny5). Organism_taxid: 11698. Expressed in: escherichia coli. Expression_system_taxid: 562

Resolution:

1.98Å R-factor: 0.238 R-free: 0.284

Authors:

K.Zadrozny,J.M.Wagner,B.K.Ganser-Pornillos,O.Pornillos

Key ref:

R.A.Dick et al. (2018). Inositol phosphates are assembly co-factors for HIV-1. Nature, 560, 509-512. PubMed id: 30069050 DOI: 10.1038/s41586-018-0396-4

Date:

31-Oct-17 Release date: 01-Aug-18

Protein chain

P12493  (GAG_HV1N5) -  Gag polyprotein from Human immunodeficiency virus type 1 group M subtype B (isolate NY5)

Seq: 500 a.a.

Struc: 207 a.a.*

* PDB and UniProt seqs differ at 2 residue positions (black crosses)

DOI no: 10.1038/s41586-018-0396-4

Nature 560:509-512 (2018)

PubMed id: 30069050

Inositol phosphates are assembly co-factors for HIV-1.

R.A.Dick, K.K.Zadrozny, C.Xu, F.K.M.Schur, T.D.Lyddon, C.L.Ricana, J.M.Wagner, J.R.Perilla, B.K.Ganser-Pornillos, M.C.Johnson, O.Pornillos, V.M.Vogt.

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 membrane^2,3. 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 inhibitors^4,5. 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.