5UPW

CryoEM Structure Refinement by Integrating NMR Chemical Shifts with Molecular Dynamics Simulations

Summary for 5UPW

• Entry DOI: 10.2210/pdb5upw/pdb
• EMDB information: 8595
• Descriptor: Gag polyprotein (1 entity in total)
• Functional Keywords: cryo-em, hiv capsid, chemical shift, molecular dynamics, hydrolase, viral protein
• Biological source: Human immunodeficiency virus type 1 (NEW YORK-5 ISOLATE)
• Cellular location: Gag polyprotein: Host cell membrane; Lipid- anchor . Matrix protein p17: Virion membrane; Lipid- anchor . Capsid protein p24: Virion . Nucleocapsid protein p7: Virion : P12493
• Total number of polymer chains: 6
• Total formula weight: 147925.61

Authors

Perilla, J.R. (deposition date: 2017-02-04, release date: 2017-03-01, Last modification date: 2022-03-30)

Primary citation

Perilla, J.R.,Zhao, G.,Lu, M.,Ning, J.,Hou, G.,Byeon, I.L.,Gronenborn, A.M.,Polenova, T.,Zhang, P.
CryoEM Structure Refinement by Integrating NMR Chemical Shifts with Molecular Dynamics Simulations.
J Phys Chem B, 121:3853-3863, 2017

PubMed Abstract: Single particle cryoEM has emerged as a powerful method for structure determination of proteins and complexes, complementing X-ray crystallography and NMR spectroscopy. Yet, for many systems, the resolution of cryoEM density map has been limited to 4-6 Å, which only allows for resolving bulky amino acids side chains, thus hindering accurate model building from the density map. On the other hand, experimental chemical shifts (CS) from solution and solid state MAS NMR spectra provide atomic level data for each amino acid within a molecule or a complex; however, structure determination of large complexes and assemblies based on NMR data alone remains challenging. Here, we present a novel integrated strategy to combine the highly complementary experimental data from cryoEM and NMR computationally by molecular dynamics simulations to derive an atomistic model, which is not attainable by either approach alone. We use the HIV-1 capsid protein (CA) C-terminal domain as well as the large capsid assembly to demonstrate the feasibility of this approach, termed NMR CS-biased cryoEM structure refinement.

PubMed: 28181439
DOI: 10.1021/acs.jpcb.6b13105

Experimental method

ELECTRON MICROSCOPY (5 Å)