5e05
Structure of Sin Nombre virus nucleoprotein in shot-axis crystal form
Structural highlights
FunctionNCAP_SINV Encapsidates the genome protecting it from nucleases (Probable). The encapsidated genomic RNA is termed the nucleocapsid (NC) and serves as template for transcription and replication (Probable). The nucleocapsid has a left-handed helical structure (By similarity). As a trimer, specifically binds and acts as a chaperone to unwind the panhandle structure formed by the viral RNA (vRNA) termini (PubMed:15650206, PubMed:15254200, PubMed:21378500, PubMed:16971445, PubMed:25062117, PubMed:16775315). Involved in the transcription and replication initiation of vRNA by mediating primer annealing (PubMed:20164193). Plays a role in cap snatching by sequestering capped RNAs in P bodies for use by the viral RdRp during transcription initiation (PubMed:19047634). Substitutes for the cellular cap-binding complex (eIF4F) to preferentially facilitate the translation of capped mRNAs (PubMed:18971945, PubMed:25062117). Initiates the translation by specifically binding to the cap and 40S ribosomal subunit (PubMed:20844026, PubMed:20164193, PubMed:25062117). Prevents the viral glycoprotein N (Gn) from autophagy-dependent breakdown maybe by blocking autophagosome formation (By similarity). Inhibits host EIF2AK2/PKR dimerization to prevent PKR-induced translational shutdown in cells and thus the activation of the antiviral state (By similarity). Also displays sequence-unspecific DNA endonuclease activity (PubMed:27261891).[UniProtKB:O36307][UniProtKB:P05133][1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] Publication Abstract from PubMedHantaviruses, which belong to the Hantavirus genus of the Bunyaviridae family, infect mammalian animals and 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 genome and form a ribonucleoprotein complex (RNP) together with viral polymerase. Here, we report the crystal structure of the core domain 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 NPcores exclude the N- and C-terminal portions of full polypeptide to get stable proteins for crystallographic study. The structure features an N-lobe and a C-lobe to clamp RNA-binding crevice, and presents two protruding extensions in both lobes. The positively charged residues located in 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. Moreover, EM visualization of native RNPs extracted from the virions revealed that a monomer-sized NP-RNA complex is the building block of viral RNP. This work provides insight into the formation of hantavirus RNP and provides an understanding of the evolutionary connections that exist amongst bunyaviruses. IMPORTANCE: Hantaviruses distribute in wide and increasing range of host reservoirs throughout the world. Particularly, hantaviruses can be transmitted via aerosols of rodent excreta to humans or human-to-human and cause HFRS and HCPS with mortalities of 15% and 50%, respectively. Hantaviruses are therefore listed as a category C pathogen. Hantavirus encodes an NP that plays essential roles both in RNP formation and in multiple biological functions. NP is also the exclusive target for the serological diagnoses. This work reveals the structure of hantavirus NP, furthering the knowledge of hantavirus RNP formation, revealing the relationship between hantavirus NP and serological specificity, and raising the potential for the development of new diagnosis and therapeutics targeting hantavirus infection. Crystal structure of the core region of hantavirus nucleocapsid protein reveals the mechanism for ribonucleoprotein complex formation.,Guo Y, Wang W, Sun Y, Ma C, Wang X, Wang X, Liu P, Shen S, Li B, Lin J, Deng F, Wang H, Lou Z J Virol. 2015 Nov 11. pii: JVI.02523-15. PMID:26559827[12] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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