Markov State Model of Lassa Virus Nucleoprotein Reveals Large Structural Changes during the Trimer to Monomer Transition
| Autor: | Eric R. May, Jason G. Pattis |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Models
Molecular Conformational change Protein Conformation Trimer medicine.disease_cause Article Viral Proteins 03 medical and health sciences chemistry.chemical_compound Molecular dynamics Protein Domains Structural Biology medicine Lassa virus Molecular Biology 030304 developmental biology Ribonucleoprotein 0303 health sciences 030302 biochemistry & molecular biology Reproducibility of Results RNA Markov Chains Nucleoprotein Nucleoproteins Monomer chemistry Biophysics sense organs Protein Multimerization |
| Zdroj: | Structure |
| ISSN: | 0969-2126 |
| DOI: | 10.1016/j.str.2020.03.002 |
| Popis: | Lassa virus contains a nucleoprotein (NP) that encapsulates the viral genomic RNA forming the ribonucleoprotein (RNP). The NP forms trimers that do not bind RNA, but a structure of only the NP N-terminal domain was co-crystallized with RNA bound. These structures suggested a model in which the NP forms a trimer to keep the RNA gate closed, but then is triggered to undergo a change to a form competent for RNA binding. Here, we investigate the scenario in which the trimer is disrupted to observe whether monomeric NP undergoes significant conformational changes. From multi-microsecond molecular dynamics simulations and an adaptive sampling scheme to sample the conformational space, a Markov state model (MSM) is constructed. The MSM reveals an energetically favorable conformational change, with the most significant changes occurring at the domain interface. These results support a model in which significant structural reorganization of the NP is required for RNP formation. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|