Title
Site-Specific Structural Variations Accompanying Tubular Assembly Of The Hiv-1 Capsid Protein
Keywords
AIDS; automated resonance assignment; electron microscopy; human immunodeficiency virus; solid-state NMR
Abstract
The 231-residue capsid (CA) protein of human immunodeficiency virus type 1 (HIV-1) spontaneously self-assembles into tubes with a hexagonal lattice that is believed to mimic the surface lattice of conical capsid cores within intact virions. We report the results of solid-state nuclear magnetic resonance (NMR) measurements on HIV-1 CA tubes that provide new information regarding changes in molecular structure that accompany CA self-assembly, local dynamics within CA tubes, and possible mechanisms for the generation of lattice curvature. This information is contained in site-specific assignments of signals in two- and three-dimensional solid-state NMR spectra, conformation-dependent 15N and 13C NMR chemical shifts, detection of highly dynamic residues under solution NMR conditions, measurements of local variations in transverse spin relaxation rates of amide 1H nuclei, and quantitative measurements of site-specific 15N-15N dipole-dipole couplings. Our data show that most of the CA sequence is conformationally ordered and relatively rigid in tubular assemblies and that structures of the N-terminal domain (NTD) and the C-terminal domain (CTD) observed in solution are largely retained. However, specific segments, including the N-terminal β-hairpin, the cyclophilin A binding loop, the inter-domain linker, segments involved in intermolecular NTD-CTD interactions, and the C-terminal tail, have substantial static or dynamical disorder in tubular assemblies. Other segments, including the 310-helical segment in CTD, undergo clear conformational changes. Structural variations associated with curvature of the CA lattice appear to be localized in the inter-domain linker and intermolecular NTD-CTD interface, while structural variations within NTD hexamers, around local 3-fold symmetry axes, and in CTD-CTD dimerization interfaces are less significant.
Publication Date
3-6-2014
Publication Title
Journal of Molecular Biology
Volume
426
Issue
5
Number of Pages
1109-1127
Document Type
Article
Personal Identifier
scopus
DOI Link
https://doi.org/10.1016/j.jmb.2013.12.021
Copyright Status
Unknown
Socpus ID
84894066520 (Scopus)
Source API URL
https://api.elsevier.com/content/abstract/scopus_id/84894066520
STARS Citation
Bayro, Marvin J.; Chen, Bo; Yau, Wai Ming; and Tycko, Robert, "Site-Specific Structural Variations Accompanying Tubular Assembly Of The Hiv-1 Capsid Protein" (2014). Scopus Export 2010-2014. 8456.
https://stars.library.ucf.edu/scopus2010/8456