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Ebola virus  Matrix protein VP40 / Ebola virus VP40

Ebola virus  Matrix protein VP40 / Ebola virus VP40 蛋白和抗體

EBOV-VP40 蛋白EBOV-VP40 抗體EBOV-VP40 基因EBOV-VP40 

Ebola virus Matrix protein VP40 / Ebola virus VP40 背景

Matrix protein VP40, the most abundant protein in ebolavirus particles, consists of 326 amino acids. It lies beneath the viral lipid envelope, where it links the envelope and the nucleocapsid together. According to the published crystal structure, VP40 polypeptide can be divided into two halves, the N- and C-terminal halves. The N-terminal half participates in VP40 oligomerization, while the C- terminal half is involved in membrane binding. Through the interactions between different N-terminal halves, VP40 can assemble into butterfly-shaped dimers. The salt bridges, polar interactions, and hydrophobic core interactions within N-terminal halves increase the stabilization of the structure. These dimers rearrange into linear hexamers by electrostatic interactions when they arriving at the cellular membrane, and then further form into a multi-layered, filamentous matrix structure. Upon the induction of urea or RNA incubation, VP40 can oligomerize into octameric ring structures, with the N- and C-terminus located at the out sides of the ring. Each octamer consists of four dimmers, and dimer-dimer interactions are primarily dependent on hydrophobic interactions. Dimer, hexamers and octamers are three distinct structures formed by unmodified wild-type VP40 and they all have unique functions in the life cycle of ebolavirus. The dimers are enssential for cellular trafficking; the hexamers take part in virus assembly; and the octamers act on virus replication, with residues such as Thr123, Phe125 and Arg134, responsible for the binding of a short single-stranded RNA. Researchers try to develop anti-Ebola drugs targeted at RNA binding pocket of VP40.

Ebola virus Matrix protein VP40 / Ebola virus VP40 參考文獻

  1. Stahelin RV. Could the Ebola virus matrix protein VP40 be a drug target? Expert Opin Ther Targets. 2014 Feb;18(2):115-20. doi: 10.1517/14728222.2014.863877.
  2. Ascenzi P, et al. Ebolavirus and Marburgvirus: insight the Filoviridae family. Mol Aspects Med. 2008 Jun;29(3):151-85.
  3. Silva LP,et al. Assembly of Ebola virus matrix protein VP40 is regulated by latch-like properties of N and C terminal tails. PLoS One. 2012;7(7):e39978. doi: 10.1371/journal.pone.0039978.
  4. Hoenen T, et al. VP40 octamers are essential for Ebola virus replication. J Virol. 2005 Feb;79(3):1898-905.
  5. Adu-Gyamfi E, et al. The Ebola virus matrix protein penetrates into the plasma membrane: a key step in viral protein 40 (VP40) oligomerization and viral egress. J Biol Chem. 2013 Feb 22;288(8):5779-89. doi: 10.1074/jbc.M112.443960.
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