Volume 14 Issue 10, October 2018

One mechanism of thalidomide teratogenicity involves binding to the CUL4–CRBN E3 ubiquitin ligase complex, which then mediates the degradation of transcription factors. New studies reveal that species-specific variants of the transcription factor SALL4 are differentially ubiquitinated and degraded via the thalidomide-bound complex.

T cell cross-reactivity enables the immune system to recognize a large array of peptides. A new study shows that T cells can achieve cross-recognition by using the remarkable plasticity of peptides, through flipping the peptide out of the binding cleft.

Duramycin is a small post-translationally modified peptide with antibody-like affinity for phosphatidylethanolamine. As it turns out, the same functionality that is essential for duramycin activity helps to catalyze the formation of its conformationally constrained and compact polycyclic architecture.

O-GlcNAcylation of translation initiation factor component eIF4GI blocks interactions to poly(A)-binding protein Pab1 to induce disassembly of stress granules, releasing Hsp70-induced mRNAs and leading to translation of protective proteins

The asymmetric cortical gradient of PAR-1 is patterned via an integration of its cortical exclusion and stabilization by a circuit consisting of aPKC and the PRBH protein PAR-2.

During the biosynthesis of the lanthipeptide duramycin, DurN catalyzes stereospecific lysinoalanine formation by preorganizing the reactive conformation of the substrate, such that one of the substrate’s own residues serves as the catalytic base.

Structural analysis shows that cross-reactivity of the T cell receptor DMF5 is governed by adaptability of the peptide antigen, which can undergo TCR-binding-induced frameshifting forcing the peptide C terminus to extend from the MHC-binding groove.

The large subunit of ribonucleotide reductase RNR-α downregulates DNA replication in the nucleus by directly disrupting PCNA and ZRANB3 interactions. RNR-α nuclear entry is regulated by an interplay between IRBIT and importin-α1.

A chemical method for site-selective deuterium exchange at protein backbone α-carbons, involving conversion of cysteine to dehydroalanine and then to deuterated cysteine, is used to explore the mechanism of a model protein bioconjugation reaction.

A new riboswitch-based RNA sensor called Riboglow binds to quenched fluorescent probes to induce fluorescence turn-on. Riboglow enables tagging and tracking of mRNA and short noncoding RNAs with different colored fluorophores in live mammalian cells.

Through use of a split-intein pIII, soluble expression phage-assisted continuous evolution (SE-PACE) enables two simultaneous positive selections to rapidly evolve proteins with improved expression while maintaining their desired activities.

Thalidomide-induced degradation of the transcription factor SALL4 in a cereblon-dependent manner provides an explanation for the teratogenic effects.