J Virol. 2015; pii: JVI.02881-14.

Vives-Adrián L, Garriga D, Buxaderas M, Fraga JS, Barbosa Pereira PJ, Macedo-Ribeiroand S, Verdaguer N.

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 β-sheet that displays striking structural similarity to the β-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.