Lepidopteran-infecting baculoviruses represent one of the most promising alternatives for pest biocontrol. In particular, Spodoptera frugiperda granulovirus (SfGV) infects the fall armyworm Spodoptera frugiperda, an increasingly important pest for maize and other crops around the world. SfGV has been investigated due to its capacity to enhance other baculovirus infectivity and as a biopesticide itself. Although the proteome of SfGV occlusion bodies (OB) is fundamental for their infectivity properties, we still lack a detailed understanding of its protein components and how they compare with other baculoviruses. To tackle this problem, we performed mass spectrometry-based proteomics analysis on SfGV OB obtained from infected larvae. We could detect 72 proteins included in SfGV OB and confirm the presence of two enhancins. EmPAI-based semiquantification highlighted the presence of two granulovirus proteins, ORF101 and ORF141, shared with other GV proteomic studies. ORF101 exhibits sequence and structural features reminiscent of the well-characterized AcMNPV P10 protein, including a coiled-coil domain and phosphorylation sites, and we confirmed its cytoplasmic aggregation through GFP-tagged expression in insect cells, suggesting a potential role in virion assembly or release. Prediction and comparison of OB protein structures allowed the detection of a common structural fold among 6 proteins PEP-1, PEP-2, PEP-P10, ORF007, ORF025, and Bro-f. Finally, comparison of four reported ODV proteomic studies of different GVs indicated that ORF040, ORF101, ORF141, and Bro-f are common components in GV OBs.

Protein phosphorylation is one of the most important posttranslational modifications altering the structure, stability, and activity of more than 13000 human proteins. In this work, the phosphotyrosine mimetic pentafluorophosphato-difluoromethyl-phenylalanine (PF5CF2Phe) was genetically encoded and incorporated into three different proteins. Screening two libraries of orthogonal aminoacyl-tRNA synthetases identified enzymes enabling the efficient and specific incorporation of PF5CF2Phe into red fluorescent protein (RFP) via amber stop codon suppression. Two model proteins, human ubiquitin (Ubq) and the B1 immunoglobulin-binding domain of streptococcal protein G (GB1), were prepared with PF5CF2Phe mutations and investigated for potential interaction partners. While native GB1 showed no binding to protein tyrosine phosphatases (PTP), PF5-GB1, with PF5CF2Phe at position 17, was a strong inhibitor of the phosphatases PTP1B and SHP2. PF5-Ubq was produced and converted into the first example of a protein carrying the most prominent phosphotyrosine mimetic, phosphono-difluoromethyl phenylalanine (PO3CF2Phe). With increasing need in the biosciences to delineate the functions of complex phosphorylation patterns, genetic encoding of PF5CF2Phe yielding phosphoprotein mimetics opens unique opportunities for precise functional studies where site-specific and homogeneous protein modifications are required.

The adapter proteins of the 14-3-3 family modulate the activity and/or localization of their binding partners, which they capture if a generic target motif is in its phosphorylated state. Here, we report the identification of potential 14-3-3 binding sites in human sirtuin deacylases by bioinformatic analysis. We then characterize the interactions of peptides representing phosphorylation sites in sirtuin 3 (pS103) and sirtuin 1 (pS670) with 14-3-3 proteins. We further describe the crystal structures of complexes of 14-3-3σ with either of the two phosphopeptides. As a conclusion, we propose a more extended 14-3-3 binding mode on the N-terminal side of the phosphorylation site and the possibility of nongeneric motifs and conformations on the C-terminal side, still resulting in the known high binding affinity of the two partners.

Integrative multi-omics profiling of a self-established cohort reveals metabolic reprogramming networks in rheumatoid arthritis.

JNK-regulated phosphoproteome links synaptic and metabolic pathways to mood regulation.

Mechanism of Houttuynia cordata in treating acute lung injury based on network pharmacology.

Structure, Function, Pathomechanisms and Targeting of TDP-43 in Neurodegeneration.

Phosphoproteomic profiling reveals PI pathway and transcription factor regulation in Tamarix hispida under salt stress.

Histamine induces vascular endothelial cell proliferation via the histamine H1 receptor-extracellular regulated protein kinase 1/2-cyclin D1/cyclin-dependent kinase 4/6 axis.

Native postsynaptic density is a functional condensate formed via phase separation.

Licochalcone B targets neural cell adhesion molecule 1 to inhibit osteosarcoma progression and ferroptosis resistance via extracellular signal-regulated kinase 5 and nuclear factor kappa B pathways.

Prunus yedoensis bark extract containing naringenin enhances hyaluronic acid synthesis and epidermal barrier function via MAPK/CREB and Akt/NF-κB pathways.

Ubiquitination of glucose and lipid metabolic proteins is altered in diabetic rat livers.

A novel GSK3β inhibitor ameliorates tau aggregation and neuroinflammation in Alzheimer's disease.

Combined network pharmacology and experimental validation reveals the mechanism of Gentiana veitchiorum Hemsl. and its active ingredient in the treatment of acute lung injury.

Single-domain protein superfamilies mediate essential signaling functions in both prokaryotes and eukaryotes. Signal transduction mediated by single-residue phosphorylation involves subtle secondary structure, side chain rotamer, and hydrogen-bond fluctuations for transitions between active and inactive conformational states, rather than large fold variations. Its study requires molecular dynamics simulations for adequate sampling of the conformational landscape. Discrimination between functional states and subfamilies is achieved by subsequent network analysis designed to couple variations at the local residue or fragment levels to functional collective motions. We describe an integrated protocol for quantitative measurement of local fluctuations and their coupling to functional motions with phosphorylation of the CheY bacterial chemotaxis signal protein as a case study.

Characterization and functional analysis of the E3 ubiquitin ligase SEVEN IN ABSENTIA like 6 in Solanum lycopersicum.

Thioredoxin interacting protein mediates corticosterone-induced depressive-like behavior in male mice.

Decoding spliceosome inhibition: Isobaric tag-based proteomic profiling of pladienolide B treated human cell lines.

Mitochondrial transplantation alleviates acute pancreatitis by suppressing macrophage necroptosis.