Structural and functional of Hantavirus nucleocapsid proteins
【摘要】：Hantaviruses, which belong to the genus Hantavirus in the family Bunyaviridae, infect mammals, including humans, causing either hemorrhagic fever with renal syndrome(HFRS) or hantavirus cardiopulmonary syndrome(HCPS) in humans with high mortality. Hantavirus encodes a nucleocapsid protein(NP) to encapsidate the genome and form a ribonucleoprotein complex(RNP) together with viral polymerase. Here, we report the crystal structure of the core domains of NP(NPcore) encoded by Sin Nombre virus(SNV) and Andes virus(ANDV), which are two representative members that cause HCPS in the New World. The constructs of SNV and ANDV NPcore exclude the N-and C-terminal portions of full polypeptide to obtain stable proteins for crystallographic study. The structure features an N lobe and a C lobe to clamp RNA-binding crevice and exhibits two protruding extensions in both lobes. The positively charged residues located in the RNA-binding crevice play a key role in RNA binding and virus replication. We further demonstrated that the C-terminal helix and the linker region connecting the N-terminal coiled-coil domain and NPcore are essential for hantavirus NP oligomerization through contacts made with two adjacent protomers. This work provides insight into the formation of hantavirus RNP and provides an understanding of the evolutionary connections that exist among bunyaviruses.