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From Proteopedia
N-terminal domain of Drosophila X Virus VP3
Structural highlights
Function[POLS_DXV96] Capsid protein VP2 self assembles to form an icosahedral capsid with a T=13 symmetry, about 70 nm in diameter, and consisting of 260 VP2 trimers. The capsid encapsulates the genomic dsRNA. VP2 is also involved in attachment and entry into the host cell (By similarity). The precursor of VP2 plays an important role in capsid assembly. First, pre-VP2 and VP2 oligomers assemble to form a procapsid. Then, the pre-VP2 intermediates may be processed into VP2 proteins by proteolytic cleavage mediated by VP4 to obtain the mature virion. The final capsid is composed of pentamers and hexamers but VP2 has a natural tendency to assemble into all-pentameric structures. Therefore pre-VP2 may be required to allow formation of the hexameric structures (By similarity). Protease VP4 is a serine protease that cleaves the polyprotein into its final products. Pre-VP2 is first partially cleaved, and may be completely processed by VP4 upon capsid maturation.[PROSITE-ProRule:PRU00881] Capsid protein VP3 plays a key role in virion assembly by providing a scaffold for the capsid made of VP2. May self-assemble to form a T=4-like icosahedral inner-capsid composed of at least 180 trimers. Plays a role in genomic RNA packaging by recruiting VP1 into the capsid and interacting with the dsRNA genome segments to form a ribonucleoprotein complex. Additionally, the interaction of the VP3 C-terminal tail with VP1 removes the inherent structural blockade of the polymerase active site. Thus, VP3 can also function as a transcriptional activator (By similarity). Structural peptide 1 is a small peptide derived from pre-VP2 C-terminus. It destabilizes and perforates cell membranes, suggesting a role during entry (By similarity). Structural peptide 2 is a small peptide derived from pre-VP2 C-terminus. It is not essential for the virus viability, but viral growth is affected when missing (By similarity). Structural peptide 3 is a small peptide derived from pre-VP2 C-terminus. It is not essential for the virus viability, but viral growth is affected when missing (By similarity). Publication Abstract from PubMedThe Birnavirus multifunctional protein VP3 plays an essential role coordinating the virus life cycle, interacting with the capsid protein VP2, with the RNA-dependent RNA polymerase VP1 and with the dsRNA genome. Furthermore, the role of this protein in controlling host cell responses triggered by dsRNA and preventing gene silencing has been recently demonstrated. Here we report the X-ray structure and dsRNA-binding activity of the N-terminal domain of Drosophila X virus (DXV) VP3. The domain folds in a bundle of three alpha-helices and arranges as a dimer, exposing to the surface a well-defined cluster of basic residues. Site directed mutagenesis combined with Electrophoretic Mobility Shift Assays (EMSA) and Surface Plasmon Resonance (SPR) revealed that this cluster, as well as a flexible and positively charged region linking the first and second globular domains of DXV VP3, are essential for dsRNA-binding. Also, RNA silencing studies performed in insect cell cultures confirmed the crucial role of this VP3 domain for the silencing suppression activity of the protein.IMPORTANCE The Birnavirus moonlighting protein VP3 plays crucial roles interacting with the dsRNA genome segments to form stable ribonucleoprotein complexes and controlling host cell immune responses, presumably by binding to and shielding the dsRNA from recognition by the host silencing machinery. The structural, biophysical and functional data presented in this work has identified the N-terminal domain of VP3 as responsible for the dsRNA-binding and silencing suppression activities of the protein in Drosophila X virus. Structure and dsRNA-binding activity of the Birnavirus Drosophila X Virus VP3 protein.,Ferrero DS, Busnadiego I, Garriga D, Guerra P, Martin MT, Kremer L, Uson I, Rodriguez JF, Verdaguer N J Virol. 2020 Nov 25. pii: JVI.02166-20. doi: 10.1128/JVI.02166-20. PMID:33239452[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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