Conformational Flexibility of the Protein-Protein Interfaces of the Ebola Virus VP40 Structural Matrix Filament

Elumalai Pavadai, Nisha Bhattarai, Prabin Baral, Robert V. Stahelin, Prem P. Chapagain, Bernard S. Gerstman

Research output: Contribution to journalArticle

Abstract

The Ebola virus (EBOV) is a virulent pathogen that causes severe hemorrhagic fever with a high fatality rate in humans. The EBOV transformer protein VP40 plays crucial roles in viral assembly and budding at the plasma membrane of infected cells. One of VP40's roles is to form the long, flexible, pleomorphic filamentous structural matrix for the virus. Each filament contains three unique interfaces: monomer NTD-NTD to form a dimer, dimer-to-dimer NTD-NTD oligomerization to form a hexamer, and end-to-end hexamer CTD-CTD to build the filament. However, the atomic-level details of conformational flexibility of the VP40 filament are still elusive. In this study, we have performed explicit-solvent, all-atom molecular dynamic simulations to explore the conformational flexibility of the three different interface structures of the filament. Using dynamic network analysis and other calculational methods, we find that the CTD-CTD hexamer interface with weak interdomain amino acid communities is the most flexible, and the NTD-NTD oligomer interface with strong interdomain communities is the least flexible. Our study suggests that the high flexibility of the CTD-CTD interface may be essential for the supple bending of the Ebola filovirus, and such flexibility may present a target for molecular interventions to disrupt the Ebola virus functioning.

Original languageEnglish (US)
JournalJournal of Physical Chemistry B
DOIs
StateAccepted/In press - Jan 1 2019
Externally publishedYes

Fingerprint

charge transfer devices
viruses
Viruses
filaments
flexibility
Dimers
proteins
Proteins
matrices
dimers
Oligomerization
Pathogens
Cell membranes
Electric network analysis
Oligomers
fever
Molecular dynamics
Amino acids
network analysis
pathogens

ASJC Scopus subject areas

  • Physical and Theoretical Chemistry
  • Surfaces, Coatings and Films
  • Materials Chemistry

Cite this

Conformational Flexibility of the Protein-Protein Interfaces of the Ebola Virus VP40 Structural Matrix Filament. / Pavadai, Elumalai; Bhattarai, Nisha; Baral, Prabin; Stahelin, Robert V.; Chapagain, Prem P.; Gerstman, Bernard S.

In: Journal of Physical Chemistry B, 01.01.2019.

Research output: Contribution to journalArticle

Pavadai, Elumalai ; Bhattarai, Nisha ; Baral, Prabin ; Stahelin, Robert V. ; Chapagain, Prem P. ; Gerstman, Bernard S. / Conformational Flexibility of the Protein-Protein Interfaces of the Ebola Virus VP40 Structural Matrix Filament. In: Journal of Physical Chemistry B. 2019.
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