Transmission electron microscopy reveals an optimal HIV-1 nucleocapsid aggregation with single-stranded nucleic acids and the mature HIV-1 nucleocapsid protein

J Mol Biol. 2006 Dec 1;364(3):496-511. doi: 10.1016/j.jmb.2006.08.065. Epub 2006 Aug 30.

Abstract

HIV-1 nucleocapsid protein (NCp7) condenses the viral RNA within the mature capsid. In a capsid-free system, NCp7 promotes an efficient mechanism of aggregation with both RNA and DNA. Here, we show an analysis of these macromolecular complexes by dark-field imaging using transmission electron microscopy. Thousands of mature NCp7 proteins co-aggregate with hundreds of single-stranded circular DNA molecules (ssDNA) within minutes, as observed with poly(rA). These co-aggregates are highly stable but dynamic structures, as they dissociate under harsh conditions, and after addition of potent ssDNA or NCp7 competitive ligands. The N-terminal domain and zinc fingers of NCp7 are both required for efficient association. Addition of magnesium slightly increases the avidity of NCp7 for ssDNA, while it strongly inhibits co-aggregation with relaxed circular double-stranded DNA (dsDNA). This DNA selectivity is restricted to mature NCp7, compared to its precursors NCp15 and NCp9. Moreover, for NCp15, the linkage of NCp7 with the Gag C-terminal p6-peptide provokes a deficiency in ssDNA aggregation, but results in DNA spreading similar to prototypical SSB proteins. Finally, this co-aggregation is discussed in a dynamic architectural context with regard to the mature HIV-1 nucleocapsid. On the basis of the present data, we propose that condensation of encapsidated RNA requires the C-terminal processing of NCp. Subsequently, disassembly of the nucleocapsid should be favoured once dsDNA is produced by HIV-1 reverse transcriptase.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Capsid Proteins / chemistry*
  • Capsid Proteins / genetics
  • Capsid Proteins / ultrastructure
  • DNA / chemistry*
  • DNA / ultrastructure
  • DNA, Single-Stranded / chemistry*
  • DNA, Single-Stranded / ultrastructure
  • Gene Products, gag / chemistry*
  • Gene Products, gag / genetics
  • Gene Products, gag / ultrastructure
  • HIV-1 / metabolism
  • Magnesium / chemistry*
  • Microscopy, Electron, Transmission
  • Nucleocapsid Proteins / chemistry*
  • Nucleocapsid Proteins / genetics
  • Nucleocapsid Proteins / ultrastructure
  • Protein Structure, Tertiary
  • Viral Proteins / chemistry*
  • Viral Proteins / genetics
  • Viral Proteins / ultrastructure
  • gag Gene Products, Human Immunodeficiency Virus

Substances

  • Capsid Proteins
  • DNA, Single-Stranded
  • Gene Products, gag
  • NCP7 protein, Human immunodeficiency virus 1
  • Nucleocapsid Proteins
  • Viral Proteins
  • gag Gene Products, Human Immunodeficiency Virus
  • p15 gag protein, Human immunodeficiency virus 1
  • DNA
  • Magnesium