Plant resistance, which acts as a selective pressure that affects viral population fitness, leads to the emergence of resistance-breaking virus strains. Most recessive resistance to potyviruses is related to the mutation of eukaryotic translation initiation factor 4E (eIF4E) or its isoforms that break their interactions with the viral genome-linked protein (VPg). In this study, we found that the VPg α1-α2 loop, which is essential for binding eIF4E, is the most variable domain of papaya ringspot virus (PRSV) VPg. PRSV VPg with the naturally occurring amino acid substitution of K105Q or E108G in the α1-α2 loop fails to interact with watermelon (Citrullus lanatus) eIF4E but interacts with watermelon eIF(iso)4E instead. Moreover, PRSV carrying these mutations can break the eIF4E-mediated resistance to PRSV in watermelon accession PI 244019. We further revealed that watermelon eIF(iso)4E with the amino acid substitutions of DNQS to GAAA in the cap-binding pocket could not interact with PRSV VPg with natural amino acid substitution of K105Q or E108G. Therefore, our finding provides a precise target for engineering watermelon germplasm resistant to resistance-breaking PRSV isolates.
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http://dx.doi.org/10.1111/mpp.70033 | DOI Listing |
Proc Natl Acad Sci U S A
January 2025
Helen Wills Neuroscience Institute, University of California Berkeley, Berkeley, CA 94720.
Norepinephrine in vertebrates and its invertebrate analog, octopamine, regulate the activity of neural circuits. We find that, when hungry, larvae switch activity in type II octopaminergic motor neurons (MNs) to high-frequency bursts, which coincide with locomotion-driving bursts in type I glutamatergic MNs that converge on the same muscles. Optical quantal analysis across hundreds of synapses simultaneously reveals that octopamine potentiates glutamate release by tonic type Ib MNs, but not phasic type Is MNs, and occurs via the G-coupled octopamine receptor (OAMB).
View Article and Find Full Text PDFProc Natl Acad Sci U S A
January 2025
Department of Psychological and Brain Sciences, Indiana University, Bloomington, IN 47405.
Dysregulation of GABAergic inhibition is associated with pathological pain. Consequently, enhancement of GABAergic transmission represents a potential analgesic strategy. However, therapeutic potential of current GABA agonists and modulators is limited by unwanted side effects.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
January 2025
Department of Chemistry and Biochemistry, The Ohio State University, Columbus, OH 43210.
The homo-dodecameric ring-shaped RNA binding attenuation protein (TRAP) from binds up to twelve tryptophan ligands (Trp) and becomes activated to bind a specific sequence in the 5' leader region of the operon mRNA, thereby downregulating biosynthesis of Trp. Thermodynamic measurements of Trp binding have revealed a range of cooperative behavior for different TRAP variants, even if the averaged apparent affinities for Trp have been found to be similar. Proximity between the ligand binding sites, and the ligand-coupled disorder-to-order transition has implicated nearest-neighbor interactions in cooperativity.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
January 2025
School of Biomolecular Science and Engineering, Vidyasirimedhi Institute of Science and Technology (VISTEC), Rayong 10120, Thailand.
A single-component flavin-dependent halogenase, AetF, has emerged as an attractive biocatalyst for catalyzing halogenation. However, its flavin chemistry remains unexplored and cannot be predicted due to its uniqueness in sequence and structure compared to other flavin-dependent monooxygenases. Here, we investigated the flavin reactions of AetF using transient kinetics.
View Article and Find Full Text PDFPLoS One
January 2025
Department of Biotechnology and Bioengineering, Chonnam National University, Gwangju, Republic of Korea.
With the advancement of genetic code expansion, the field is progressing towards incorporating multiple non-canonical amino acids (ncAAs). The specificity of aminoacyl-tRNA synthetases (aaRSs) towards ncAAs is a critical factor, as engineered aaRSs frequently show polyspecificity, complicating the precise incorporation of multiple ncAAs. To address this challenge, predicting binding affinity can be beneficial.
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