title: Conserved proline-rich region of Ebola virus matrix protein VP40 is essential for plasma membrane targeting and virus-like particle release.
abstract: The matrix protein VP40 is essential for Ebola virus (EBOV) and Marburg virus assembly and budding at the plasma membrane. In this study we have investigated the effect of single amino acid substitutions in a conserved proline-rich region of the EBOV VP40 located in the carboxy-terminal part of the protein. We demonstrate that substitutions within this region result in an alteration of intracellular VP40 localization and also cause a reduction or a complete block of virus-like particle budding, a benchmark of VP40 function. Furthermore, some mutated VP40s revealed an enhanced binding with cellular Sec24C, a part of the coat protein complex II (COPII) vesicular transport system. Analysis of the 3-dimensional structure of VP40 revealed the spatial proximity of the proline-rich region and an earlier identified site of interaction with Sec24C, thus allowing us to hypothesize that the altered intracellular localization of the VP40 mutants is a consequence of defects in their interaction with COPII-mediated vesicular transport.
authors: Filovirus Laboratory, INSERM U758, Human Virology Department, Claude Bernard Université Lyon 1, Ecole Normale Supérieure de Lyon, Lyon, France.
authors: Olivier
authors: O
authors: Reynard
authors: Kirill
authors: K
authors: Nemirov
authors: Audrey
authors: A
authors: Page
authors: Mathieu
authors: M
authors: Mateo
authors: Hervé
authors: H
authors: Raoul
authors: Winfried
authors: W
authors: Weissenhorn
authors: Viktor E
authors: VE
authors: Volchkov
mesh_terms: D000818:Animals; D002462:Cell Membrane / Q000378:metabolism*; D002522:Chlorocebus aethiops; D029043:Ebolavirus / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D008958:Models, Molecular; D015739:Nocodazole / Q000494:pharmacology; D011392:Proline / Q000737:chemistry*; D011487:Protein Conformation; D021381:Protein Transport; D050257:Tubulin Modulators / Q000494:pharmacology; D014709:Vero Cells; D014763:Viral Matrix Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D057074:Virus Release / Q000502:physiology*
chemical_list: D050257:Tubulin Modulators; C080981:VP40 protein, virus; D014763:Viral Matrix Proteins; D011392:Proline; D015739:Nocodazole