G-quartets direct assembly of HIV-1 nucleocapsid protein along single-stranded DNA

Nucleic Acids Res. 2003 Oct 1;31(19):5754-63. doi: 10.1093/nar/gkg716.


The d(TTGGGGGGTACAGTGCA) sequence, derived from the human immunodeficiency virus type 1 (HIV-1) central DNA flap, can form in vitro an intermolecular parallel DNA quadruplex. This work demonstrates that the HIV-1 nucleocapsid protein (NCp) exhibits a high affinity (10(8) M(-1)) for this quadruplex. This interaction is predominantly hydrophobic, maintained by a stabilization between G-quartet planes and the C-terminal zinc finger of the protein. It also requires 5 nt long tails flanking the quartets plus both the second zinc-finger and the N-terminal domain of NCp. The initial binding nucleates an ordered arrangement of consecutive NCp along the four single-stranded tails. Such a process requires the N-terminal zinc finger, and was found to occur for DNA site sizes shorter than usual in a sequence-dependent manner. Concurrently, NCp binding is efficient on a G'2 quadruplex also derived from the HIV-1 central DNA flap. Apart from their implication within the DNA flap, these data lead to a model for the nucleic acid architecture within the viral nucleocapsid, where adjacent single-stranded tails and NCp promote a compact assembly of NCp and nucleic acid growing from stably and primary bound NCp.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Base Sequence
  • Binding Sites
  • Capsid Proteins / chemistry
  • Capsid Proteins / metabolism*
  • DNA / chemistry*
  • DNA / metabolism*
  • DNA, Single-Stranded / chemistry
  • DNA, Single-Stranded / metabolism*
  • G-Quadruplexes
  • Gene Products, gag / chemistry
  • Gene Products, gag / genetics
  • Gene Products, gag / metabolism*
  • Guanine / chemistry*
  • HIV-1*
  • Macromolecular Substances
  • Models, Biological
  • Nucleic Acid Conformation
  • Protein Binding
  • Protein Precursors / genetics
  • Protein Precursors / metabolism
  • Protein Structure, Tertiary
  • Recombinant Proteins / analysis


  • Capsid Proteins
  • DNA, Single-Stranded
  • Gene Products, gag
  • Macromolecular Substances
  • Protein Precursors
  • Recombinant Proteins
  • p55 gag precursor protein, Human immunodeficiency virus 1
  • Guanine
  • DNA