Backbone dynamics of the N-terminal domain of the HIV-1 capsid protein and comparison with the G94D mutant conferring cyclosporin resistance/dependence - PubMed (original) (raw)

Comparative Study

. 1999 Aug 10;38(32):10262-71.

doi: 10.1021/bi990991x.

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Comparative Study

Backbone dynamics of the N-terminal domain of the HIV-1 capsid protein and comparison with the G94D mutant conferring cyclosporin resistance/dependence

R Campos-Olivas et al. Biochemistry. 1999.

Abstract

Nuclear magnetic resonance (NMR) (15)N relaxation methods have been used to characterize the backbone dynamics of the N-terminal core domain of the HIV-1 capsid protein (CA(151)). The domain, which has an unusually flat, triangular shape, tumbles in solution at 28 degrees C with an effective rotational correlation time of 11.5 ns. Relaxation data for backbone amides in the domain's seven alpha-helices are indicative of fully anisotropic rotational diffusion. The principal axes of the rotational diffusion tensor calculated from the NMR data are aligned to within 12-23 degrees of the principal axes of the inertial tensor, with the axis of fastest rotational diffusion coincident with that of minimal inertia, and vice versa. Large variations in the (15)N-(1)H nuclear Overhauser effects for individual amino acids correlate with the degree of convergence in the previously calculated NMR structure. In particular, the partially disordered residues Val86-Arg97 that contain the human cyclophilin A (CypA) packaging signal have (15)N heteronuclear NOEs and transversal relaxation rates consistent with a high degree of dynamic conformational averaging. The N-terminal domain of a CA mutant (G94D) that confers both resistance to and dependence on cyclosporin A analogues was also analyzed. Our results indicate that this mutation does not influence the conformation or dynamics of CA(151), and therefore probably affects the function of the protein by modifying essential intermolecular CA-CA interactions.

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