PROSITE documentation PDOC52107

Filovirus VP40 matrix protein profile

The filovirus family includes viruses such as Ebola and Marburg viruses that can cause hemorrhagic fever and severe disease [E1]. Filoviruses package their single-stranded negative-sense RNA genomes with viral proteins including nucleoprotein (NP), VP24 and VP35, into helical ribonucleoprotein assemblies called nucleocapsids (NCs). NCs are recruited to the plasma membrane and bud from the host cells as enveloped virions with a characteristic filamentous morphology from which the family takes its name. The filovirus matrix protein, VP40, binds to and concentrates at the plasma membrane of infected cells, where it can interact with components of the NC to promote envelopment, and where it drives formation of the filamentous virus particles. In addition, VP40 has been shown to regulate viral replication and transcription [1,2,3,4,5].

Filovirus VP40 consists of an N-terminal domain (NTD) involved in homo-oligomerization and a C-terminal domain (CTD) that is crucial for the interaction with membranes. The domains are connected by a flexible linker, which allows movement between the NTD and CTD. Both the N- and C-terminal domains fold into similar β-sandwich structures, suggesting that they might have been generated by gene duplication. The NTD contains a β sandwich decorated by four small α helices, whereas the CTD contains some disordered loop structure that links two small β sheets and two α helices (see <PDB:4LD8>). There is a disulfide bond between the two C-terminal cysteines of ebolavirus CTDs. The limited number of contacts observed between the NTD and CTD suggests that they are tenuously connected and could separate to assemble a different structure. The highly plastic VP40 polypeptide is able to rearrange itself into distinct structural assemblies. Each of these distinct structures is assembled by the unmodified wild-type polypeptide, and each structure is required for a separate and essential function in the filovirus life cycle. A butterfly-shaped VP40 dimer traffics to the cellular membrane. Once there, electrostatic interactions trigger rearrangement of the polypeptide into a hexameric structural component for the viral matrix assembly. A third structure of VP40, a ring-shaped octamer, is not involved in virus assembly but instead uniquely binds RNA to regulate viral transcription inside infected cells [1,2,3,4,5].

The profile we developed for the Filovirus VP40 protein covers the N- and C-terminal domains.