Structure of the N-terminal 283-residue Fragment of the Immature HIV-1 Gag Polyprotein

Nat Struct Biol. 2002 Jul;9(7):537-43. doi: 10.1038/nsb806.

Abstract

The capsid protein (CA) of the mature human immunodeficiency virus (HIV) contains an N-terminal beta-hairpin that is essential for formation of the capsid core particle. CA is generated by proteolytic cleavage of the Gag precursor polyprotein during viral maturation. We have determined the NMR structure of a 283-residue N-terminal fragment of immature HIV-1 Gag (Gag(283)), which includes the intact matrix (MA) and N-terminal capsid (CA(N)) domains. The beta-hairpin is unfolded in Gag(283), consistent with the proposal that hairpin formation occurs subsequent to proteolytic cleavage of Gag, triggering capsid assembly. Comparison of the immature and mature CA(N) structures reveals that beta-hairpin formation induces a approximately 2 A displacement of helix 6 and a concomitant displacement of the cyclophylin-A (CypA)-binding loop, suggesting a possible allosteric mechanism for CypA-mediated destabilization of the capsid particle during infectivity.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Cyclophilin A / metabolism
  • Gene Products, gag / chemistry*
  • Gene Products, gag / metabolism
  • HIV Antigens / chemistry
  • HIV-1 / chemistry*
  • HIV-1 / growth & development
  • HIV-1 / physiology
  • HIV-1 / ultrastructure
  • Hydrogen Bonding
  • Hydrophobic and Hydrophilic Interactions
  • Models, Molecular
  • Molecular Sequence Data
  • Nuclear Magnetic Resonance, Biomolecular
  • Nucleocapsid Proteins*
  • Peptide Fragments / chemistry*
  • Peptide Fragments / metabolism
  • Protein Precursors / chemistry*
  • Protein Precursors / metabolism
  • Protein Structure, Secondary
  • Protein Structure, Tertiary
  • Viral Proteins*
  • Virus Assembly
  • gag Gene Products, Human Immunodeficiency Virus

Substances

  • Gene Products, gag
  • HIV Antigens
  • Nucleocapsid Proteins
  • Peptide Fragments
  • Protein Precursors
  • Viral Proteins
  • gag Gene Products, Human Immunodeficiency Virus
  • p15 gag protein, Human immunodeficiency virus 1
  • p17 protein, Human Immunodeficiency Virus Type 1
  • p55 gag precursor protein, Human immunodeficiency virus 1
  • Cyclophilin A

Associated data

  • PDB/1GWP
  • PDB/1L6N