9ogq | pdb_00009ogq

Rotavirus NSP2 K294E mutant

spinqualitylabelsall models 9ogq, resolution 2.25Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 9ogq is a 1 chain structure with sequence from Rotavirus A. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.25Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function NSP2_ROTSR Involved in genome replication and packaging. Plays a crucial role, together with NSP5, in the formation of virus factories (viroplasms) which are large inclusions in the cytoplasm where replication intermediates are assembled and RNA replication takes place. Displays ssRNA binding, NTPase, RNA triphosphatase (RTPase) and ATP-independent helix-unwinding activity activities. The unwiding activity may prepare and organize plus-strand RNAs for packaging and replication by removing interfering secondary structures. Unlike typical helicases, NSP2 requires neither a divalent cation nor a nucleotide energy source for helix destabilization. The RTPase activity may account for the absence of the 5'-terminal gamma-phosphate on the minus-strands of dsRNA genome segments (By similarity). Publication Abstract from PubMed Rotaviruses (RVs) induce the formation of cytoplasmic viral factories, termed viroplasms, which are the sites of early particle assembly and viral RNA synthesis. The RV octameric nonstructural protein 2 (NSP2) plays critical, albeit incompletely understood, roles during viroplasm biogenesis. Previous work by our lab demonstrated that a RV bearing a lysine-to-glutamic acid (K294E) change in the flexible C-terminus of NSP2 exhibits defects in viral replication and induces smaller, more numerous viroplasms as compared to the wildtype (WT) virus. In this study, we sought to better understand if/how this K294E amino acid change altered the structure and/or dynamics of the NSP2 protein. We first determined the X-ray crystal structures of untagged, recombinant NSP2(K294E) and NSP2(WT). We found that both proteins formed highly similar octamers and crystallized in the I422 space group. To better understand the possible impacts of the K294E change on the conformations and backbone flexibility of NSP2, we performed molecular dynamics simulations. The results showed that NSP2(K294E) adopted distinct C-terminal conformations relative to NSP2(WT) and had subtle flexibility differences. Most notably, the data suggest that the K294E change stabilized a rare C-terminal conformation that was only infrequently sampled by NSP2(WT). This shift in conformational preference may help explain why NSP2(K294E) displayed decreased capacity to mediate robust viroplasm formation during RV infection. These results provide mechanistic insights into how a single amino acid change in the NSP2 C-terminus can have large effects on structural ensemble, shedding light on features of the protein that underpin RV viroplasm formation. K294E change in the rotavirus factory forming protein NSP2 stabilizes a rare C-terminal conformation.,Nichols SL, Hollis T, Salsbury FR, Esstman SM J Biomol Struct Dyn. 2025 Sep 26:1-17. doi: 10.1080/07391102.2025.2563689. PMID:40999894 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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