6w0l

Henipavirus W protein interacts with 14-3-3 to modulate host gene expression

spinqualitylabelsall models 6w0l, resolution 2.30Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6w0l is a 2 chain structure with sequence from Homo sapiens and Pteropus alecto. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.3Å Ligands: CA, SEP Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function 1433S_HUMAN Adapter protein implicated in the regulation of a large spectrum of both general and specialized signaling pathways. Binds to a large number of partners, usually by recognition of a phosphoserine or phosphothreonine motif. Binding generally results in the modulation of the activity of the binding partner. When bound to KRT17, regulates protein synthesis and epithelial cell growth by stimulating Akt/mTOR pathway (By similarity). p53-regulated inhibitor of G2/M progression. Publication Abstract from PubMed Nipah (NiV) and Hendra virus (HeV), members of the henipavirus genus in the Paramyxoviridae family, are recently emerged, highly lethal zoonotic pathogens. The NiV and HeV non-segmented, negative-sense RNA genomes encode for nine proteins, including the W protein. Expressed from the P gene through mRNA editing, W shares a common N-terminus with P and V, but has a unique C-terminus. Expressed alone, W modulates innate immune responses by several mechanisms and elimination of W from NiV alters the course of infection in experimentally-infected-ferrets. However, the specific host interactions that allow W to modulate innate immunity are incompletely understood. This study demonstrates that the NiV and HeV W proteins interact with all seven isoforms of the 14-3-3 family, regulatory molecules that preferentially bind phosphorylated target proteins to regulate a wide range of cellular functions. The interaction is dependent on the penultimate amino acid residue in the W sequence, a conserved, phosphorylated serine. The co-crystal structure of the W C-terminal binding motif with 14-3-3 provides only the second structure of a complex containing a mode III interactor, which is defined as a 14-3-3 interaction with a phosphoserine/phosphothreonine at the C-termini of the target protein. Transcriptomic analysis of inducible cell lines infected with an RNA virus and expressing either wildtype W or W lacking 14-3-3 binding, identifies new functions for W. These include the regulation of cellular metabolic processes, cell junction organization and apoptosis.IMPORTANCE Nipah (NiV) and Hendra virus (HeV), members of the Henipavirus genus, are recently emerged, highly lethal zoonotic pathogens that cause yearly outbreaks. NiV and HeV each encode a W protein that has roles in regulating host signaling pathways, including antagonism of the innate immune response. However, the mechanisms used by W to regulate these host responses are not clear. Here, characterization of the interaction of NiV and HeV W with 14-3-3 identifies modulation of 14-3-3 regulated host signaling pathways not previously associated with W, suggesting new avenues of research. The co-crystal structure of the NiV W:14-3-3 complex, as only the second structure of a 14-3-3 mode III interactor, provides further insight into this less well understood 14-3-3 binding motif. Henipavirus W proteins interact with 14-3-3 to modulate host gene expression.,Edwards MR, Hoad M, Tsimbalyuk S, Menicucci AR, Messaoudi I, Forwood JK, Basler CF J Virol. 2020 Apr 22. pii: JVI.00373-20. doi: 10.1128/JVI.00373-20. PMID:32321809 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also 14-3-3 protein 3D structures

Proteopedia Page Contributors and Editors (what is this?)

OCA