Proteomic elucidation of the targets and primary functions of the picornavirus 2A protease.

Autor:	Serganov AA; Laboratory of Cellular and Structural Biology, The Rockefeller University, New York, New York, USA., Udi Y; Laboratory of Cellular and Structural Biology, The Rockefeller University, New York, New York, USA. Electronic address: yudi@rockefeller.edu., Stein ME; Laboratory of Cellular and Structural Biology, The Rockefeller University, New York, New York, USA., Patel V; Laboratory of Cellular and Structural Biology, The Rockefeller University, New York, New York, USA., Fridy PC; Laboratory of Cellular and Structural Biology, The Rockefeller University, New York, New York, USA., Rice CM; Laboratory of Virology and Infectious Disease, The Rockefeller University, New York, New York, USA., Saeed M; Laboratory of Virology and Infectious Disease, The Rockefeller University, New York, New York, USA; Department of Biochemistry, Boston University School of Medicine, Boston, Massachusetts, USA; National Emerging Infectious Diseases Laboratories, Boston University School of Medicine, Boston University, Massachusetts, USA. Electronic address: msaeed1@bu.edu., Jacobs EY; Laboratory of Mass Spectrometry and Gaseous Ion Chemistry, The Rockefeller University, New York, New York, USA; Chemistry Department, St John's University, Queens, New York, USA. Electronic address: jacobse@stjohns.edu., Chait BT; Laboratory of Mass Spectrometry and Gaseous Ion Chemistry, The Rockefeller University, New York, New York, USA. Electronic address: chait@rockefeller.edu., Rout MP; Laboratory of Cellular and Structural Biology, The Rockefeller University, New York, New York, USA. Electronic address: rout@rockefeller.edu.
Jazyk:	angličtina
Zdroj:	The Journal of biological chemistry [J Biol Chem] 2022 Jun; Vol. 298 (6), pp. 101882. Date of Electronic Publication: 2022 Mar 31.
DOI:	10.1016/j.jbc.2022.101882
Abstrakt:	Picornaviruses are small RNA viruses that hijack host cell machinery to promote their replication. During infection, these viruses express two proteases, 2A pro and 3C pro , which process viral proteins. They also subvert a number of host functions, including innate immune responses, host protein synthesis, and intracellular transport, by utilizing poorly understood mechanisms for rapidly and specifically targeting critical host proteins. Here, we used proteomic tools to characterize 2A pro interacting partners, functions, and targeting mechanisms. Our data indicate that, initially, 2A pro primarily targets just two cellular proteins: eukaryotic translation initiation factor eIF4G (a critical component of the protein synthesis machinery) and Nup98 (an essential component of the nuclear pore complex, responsible for nucleocytoplasmic transport). The protease appears to employ two different cleavage mechanisms; it likely interacts with eIF3L, utilizing the eIF3 complex to proteolytically access the eIF4G protein but also directly binds and degrades Nup98. This Nup98 cleavage results in only a marginal effect on nuclear import of proteins, while nuclear export of proteins and mRNAs were more strongly affected. Collectively, our data indicate that 2A pro selectively inhibits protein translation, key nuclear export pathways, and cellular mRNA localization early in infection to benefit viral replication at the expense of particular cell functions. Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article. (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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