title: Investigation of the structure and dynamics of the capsid-spacer peptide 1-nucleocapsid fragment of the HIV-1 gag polyprotein by solution NMR spectroscopy.
abstract: Structural studies of HIV-1 Gag, the primary structural polyprotein involved in retroviral assembly, have been challenging, owing to its flexibility and conformational heterogeneity. Using residual dipolar couplings, we show that the four structural units of the capsid (CA)-spacer peptide 1 (SP1)-nucleocapsid (NC) fragment of HIV-1 Gag (namely, the N- and C-terminal domains of capsid, and the N- and C-terminal Zn knuckles of nucleocapsid) have the same structures as their individually isolated counterparts, and tumble semi-independently of one another in the absence of nucleic acids. Nucleic acids bind exclusively to the nucleocapsid domain and fix the orientation of the two Zn knuckles relative to one another so that the nucleocapsid domain/nucleic acid complex behaves as a single structural unit. The low (15) N-{(1) H} heteronuclear NOE values (≤0.4), the close to zero values for the residual dipolar couplings of the backbone amides, and minimal deviations from random-coil chemical shifts for the C-terminal tail of capsid and SP1, both in the absence and presence of nucleic acids, indicate that these regions are intrinsically disordered in the context of CA-SP1-NC.
authors: Laboratories of Chemical Physics and Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892-0520 (USA).
authors: Lalit
authors: L
authors: Deshmukh
authors: Rodolfo
authors: R
authors: Ghirlando
authors: G Marius
authors: GM
authors: Clore
mesh_terms: D036022:Capsid Proteins / Q000737:chemistry*; D019906:Nuclear Magnetic Resonance, Biomolecular; D011487:Protein Conformation; D012996:Solutions; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000737:chemistry*
chemical_list: D036022:Capsid Proteins; D012996:Solutions; D054301:gag Gene Products, Human Immunodeficiency Virus
keywords: molecular dynamics; nucleic acids; proteins; residual dipolar couplings; viruses