4D1K

Cryo-electron microscopy of tubular arrays of HIV-1 Gag resolves structures essential for immature virus assembly.

Summary for 4D1K

• Entry DOI: 10.2210/pdb4d1k/pdb
• Related: 4COC
• EMDB information: 2638
• Descriptor: GAG PROTEIN (1 entity in total)
• Functional Keywords: viral protein, capsid, sp1, helical reconstruction
• Biological source: HUMAN IMMUNODEFICIENCY VIRUS 1
• Total number of polymer chains: 6
• Total formula weight: 146531.93

Authors

Bharat, T.A.M.,Castillo-Menendez, L.R.,Hagen, W.J.H.,Lux, V.,Igonet, S.,Schorb, M.,Schur, F.K.M.,Krauesslich, H.G.,Briggs, J.A.G. (deposition date: 2014-05-02, release date: 2014-06-04, Last modification date: 2024-05-08)

Primary citation

Bharat, T.A.M.,Castillo Menendez, L.R.,Hagen, W.J.H.,Lux, V.,Igonet, S.,Schorb, M.,Schur, F.K.M.,Krausslich, H.,Briggs, J.A.G.
Cryo-Electron Microscopy of Tubular Arrays of HIV-1 Gag Resolves Structures Essential for Immature Virus Assembly.
Proc.Natl.Acad.Sci.USA, 111:8233-, 2014

PubMed Abstract: The assembly of HIV-1 is mediated by oligomerization of the major structural polyprotein, Gag, into a hexameric protein lattice at the plasma membrane of the infected cell. This leads to budding and release of progeny immature virus particles. Subsequent proteolytic cleavage of Gag triggers rearrangement of the particles to form mature infectious virions. Obtaining a structural model of the assembled lattice of Gag within immature virus particles is necessary to understand the interactions that mediate assembly of HIV-1 particles in the infected cell, and to describe the substrate that is subsequently cleaved by the viral protease. An 8-Å resolution structure of an immature virus-like tubular array assembled from a Gag-derived protein of the related retrovirus Mason-Pfizer monkey virus (M-PMV) has previously been reported, and a model for the arrangement of the HIV-1 capsid (CA) domains has been generated based on homology to this structure. Here we have assembled tubular arrays of a HIV-1 Gag-derived protein with an immature-like arrangement of the C-terminal CA domains and have solved their structure by using hybrid cryo-EM and tomography analysis. The structure reveals the arrangement of the C-terminal domain of CA within an immature-like HIV-1 Gag lattice, and provides, to our knowledge, the first high-resolution view of the region immediately downstream of CA, which is essential for assembly, and is significantly different from the respective region in M-PMV. Our results reveal a hollow column of density for this region in HIV-1 that is compatible with the presence of a six-helix bundle at this position.

PubMed: 24843179
DOI: 10.1073/PNAS.1401455111

Experimental method

ELECTRON MICROSCOPY (9.4 Å)