Structural basis for host membrane remodeling induced by protein 2B of hepatitis A virus

Laila Vives-Adrian, Damia Garriga, Monica Buxaderas, Joana S Fraga, Pedro J B Pereira, Sandra Macedo-Ribeiro, Nuria Verdaguer

Research output: Contribution to journalArticleResearchpeer-review

6 Citations (Scopus)

Abstract

The complexity of viral RNA synthesis and the numerous participating factors require a mechanism to topologically coordinate and concentrate these multiple viral and cellular components, ensuring a concerted function. Similar to all other positive-strand RNA viruses, picornaviruses induce rearrangements of host intracellular membranes to create structures, which act as functional scaffolds for genome replication. The membrane-targeting proteins 2B, 2C, their precursor 2BC, and protein 3A appear primarily involved in membrane remodeling. Little is known about the structure of these proteins and the mechanisms by which they induce massive membrane remodeling. Here we report the crystal structure of the soluble region of hepatitis A virus (HAV) protein 2B, consisting of two domains: a C-terminal helical bundle, preceded by a N-terminal curved five-stranded anti-parallel beta-sheet that displays striking structural similarity to the beta-barrel domain of enteroviral 2A proteins. Moreover, the helicoidal arrangement of the protein molecules in the crystal provides a model for 2B-induced host membrane remodeling during HAV infection. IMPORTANCE: No structural information is currently available for the 2B protein of any picornavirus, despite being involved in a critical process in viral factories formation: the rearrangement of host intracellular membranes. Here we present the structure of the soluble domain of the 2B protein of HepatititsA virus (HAV). Its arrangement, both in crystals and in solution under physiological conditions can help to understand its function and sheds some light on the membrane rearrangement process, a putative target of future antiviral drugs. Moreover, this first structure of a picornaviral2B protein also unveils a closer evolutionary relationship between the hepatovirus and enterovirus genres within the Picornaviridae family.
Original languageEnglish
Pages (from-to)3648 - 3658
Number of pages11
JournalJournal of Virology
Volume89
Issue number7
DOIs
Publication statusPublished - 2015

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