7ZUD

Crystal structure of HIV-1 capsid IP6-CPSF6 complex

Summary for 7ZUD

• Entry DOI: 10.2210/pdb7zud/pdb
• Descriptor: Capsid protein p24, Cleavage and polyadenylation specificity factor subunit 6, INOSITOL HEXAKISPHOSPHATE, ... (4 entities in total)
• Functional Keywords: complex, cofactor, host-factor, viral protein
• Biological source: Human immunodeficiency virus 1; More
• Total number of polymer chains: 2
• Total formula weight: 28404.20

Authors

Nicastro, G.,Taylor, I.A. (deposition date: 2022-05-12, release date: 2022-07-27, Last modification date: 2024-10-23)

Primary citation

Nicastro, G.,Lucci, M.,Oregioni, A.,Kelly, G.,Frenkiel, T.A.,Taylor, I.A.
CP-MAS and Solution NMR Studies of Allosteric Communication in CA-assemblies of HIV-1.
J.Mol.Biol., 434:167691-167691, 2022

PubMed Abstract: Solution and solid-state NMR spectroscopy are highly complementary techniques for studying structure and dynamics in very high molecular weight systems. Here we have analysed the dynamics of HIV-1 capsid (CA) assemblies in presence of the cofactors IP6 and ATPγS and the host-factor CPSF6 using a combination of solution state and cross polarisation magic angle spinning (CP-MAS) solid-state NMR. In particular, dynamical effects on ns to µs and µs to ms timescales are observed revealing diverse motions in assembled CA. Using CP-MAS NMR, we exploited the sensitivity of the amide/Cα-Cβ backbone chemical shifts in DARR and NCA spectra to observe the plasticity of the HIV-1 CA tubular assemblies and also map the binding of cofactors and the dynamics of cofactor-CA complexes. In solution, we measured how the addition of host- and co-factors to CA -hexamers perturbed the chemical shifts and relaxation properties of CA-Ile and -Met methyl groups using transverse-relaxation-optimized NMR spectroscopy to exploit the sensitivity of methyl groups as probes in high-molecular weight proteins. These data show how dynamics of the CA protein assembly over a range of spatial and temporal scales play a critical role in CA function. Moreover, we show that binding of IP6, ATPγS and CPSF6 results in local chemical shift as well as dynamic changes for a significant, contiguous portion of CA, highlighting how allosteric pathways communicate ligand interactions between adjacent CA protomers.

PubMed: 35738429
DOI: 10.1016/j.jmb.2022.167691

Experimental method

X-RAY DIFFRACTION (2.93 Å)