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J Am Chem Soc. 2016 Sep 21;138(37):12029-32. doi: 10.1021/jacs.6b07259. Epub 2016 Sep 7.

Helical Conformation in the CA-SP1 Junction of the Immature HIV-1 Lattice Determined from Solid-State NMR of Virus-like Particles.

Author information

1
Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health , Bethesda, Maryland 20892-0520, United States.
2
Department of Molecular Physiology and Biological Physics, University of Virginia School of Medicine , Seridan G. Snyder Translational Research Building, 480 Ray C. Hunt Drive, Charlottesville, Virginia 22908, United States.
3
Department of Medicine, Division of Cardiovascular Medicine, University of Virginia Health System , Charlottesville, Virginia 22908, United States.
4
Center for Membrane and Cell Physiology, University of Virginia School of Medicine , Charlottesville, Virginia 22908, United States.

Abstract

Maturation of HIV-1 requires disassembly of the Gag polyprotein lattice, which lines the viral membrane in the immature state, and subsequent assembly of the mature capsid protein lattice, which encloses viral RNA in the mature state. Metastability of the immature lattice has been proposed to depend on the existence of a structurally ordered, α-helical segment spanning the junction between capsid (CA) and spacer peptide 1 (SP1) subunits of Gag, a segment that is dynamically disordered in the mature capsid lattice. We report solid state nuclear magnetic resonance (ssNMR) measurements on the immature lattice in noncrystalline, spherical virus-like particles (VLPs) derived from Gag. The ssNMR data provide definitive evidence for this critical α-helical segment in the VLPs. Differences in ssNMR chemical shifts and signal intensities between immature and mature lattice assemblies also support a major rearrangement of intermolecular interactions in the maturation process, consistent with recent models from electron cryomicroscopy and X-ray crystallography.

PMID:
27593947
PMCID:
PMC5636003
DOI:
10.1021/jacs.6b07259
[Indexed for MEDLINE]
Free PMC Article

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