Ebola virus protein VP40 binding to Sec24c for transport to the plasma membrane.
Nisha Bhattarai, Elumalai Pavadai, Rudramani Pokhrel, Prabin Baral, Md Lokman Hossen, Robert V Stahelin, Prem P Chapagain, Bernard S Gerstman
Author Information
Nisha Bhattarai: Department of Physics, Florida International University, Miami, Florida, USA.
Elumalai Pavadai: Department of Physics, Florida International University, Miami, Florida, USA.
Rudramani Pokhrel: Department of Physics, Florida International University, Miami, Florida, USA.
Prabin Baral: Department of Physics, Florida International University, Miami, Florida, USA.
Md Lokman Hossen: Department of Physics, Florida International University, Miami, Florida, USA.
Robert V Stahelin: Department of Medicinal Chemistry & Molecular Pharmacology and the Purdue Institute of Inflammation, Immunology and Infectious Disease, Purdue University, West Lafayette, Indiana, USA.
Prem P Chapagain: Department of Physics, Florida International University, Miami, Florida, USA.
Bernard S Gerstman: Department of Physics, Florida International University, Miami, Florida, USA. ORCID
Outbreaks of the Ebola virus (EBOV) continue to occur and while a vaccine and treatment are now available, there remains a dearth of options for those who become sick with EBOV disease. An understanding at the atomic and molecular level of the various steps in the EBOV replication cycle can provide molecular targets for disrupting the virus. An important step in the EBOV replication cycle is the transport of EBOV structural matrix VP40 protein molecules to the plasma membrane inner leaflet, which involves VP40 binding to the host cell's Sec24c protein. Though some VP40 residues involved in the binding are known, the molecular details of VP40-Sec24c binding are not known. We use various molecular computational techniques to investigate the molecular details of how EBOV VP40 binds with the Sec24c complex of the ESCRT-I pathway. We employed different docking programs to identify the VP40-binding site on Sec24c and then performed molecular dynamics simulations to determine the atomic details and binding interactions of the complex. We also investigated how the inter-protein interactions of the complex are affected upon mutations of VP40 amino acids in the Sec24c-binding region. Our results provide a molecular basis for understanding previous coimmunoprecipitation experimental studies. In addition, we found that VP40 can bind to a site on Sec24c that can also bind Sec23 and suggests that VP40 may use the COPII transport mechanism in a manner that may not need the Sec23 protein in order for VP40 to be transported to the plasma membrane.
