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  • Membrane-less organelles formed by liquid–liquid phase separation provide additional cellular compartmentalization for precise spatiotemporal regulation of biological processes. Ke Ruan, Yi Lin, Peiguo Yang and Wen Zhou report on the formation, regulation and function of biomolecular condensates, discussed at the 2023 Xiangshan Science Conference on Membrane-less Organelles.

    • Ke Ruan
    • Yi Lin
    • Wen Zhou
    Meeting Report
  • The susceptibility of nitric oxide (NO) to scavenging and oxidation limits its bioavailability and signaling role. New studies indicate that a NO–ferroheme adduct is resistant to such constraints and may serve as an alternative NO-derived signaling molecule in vasculature.

    • Emil Martin
    News & Views
  • Nitric oxide (NO) is a potent vascular signaling agent, but its bioavailability is limited through rapid scavenging reactions. DeMartino et al. characterize the formation and bioactivity of NO-ferroheme, a stable NO analog that forms readily, bypasses scavenging reactions and mediates NO signaling.

    • Anthony W. DeMartino
    • Laxman Poudel
    • Daniel B. Kim-Shapiro
  • Questions remain on the nature of the bioactivity of nitric oxide (NO) synthase signaling despite its wide appreciation. Here the authors describe NO-ferroheme as a vascular signaling species, whose biological activity is unrelated to the release of free nitric oxide, but allows it to travel protected to its main target guanylyl cyclase.

    • Andrei L. Kleschyov
    • Zhengbing Zhuge
    • Jon O. Lundberg
    ArticleOpen Access
  • By investigating the structure–activity relationship of molecular glue degraders that target cyclin K, we discovered that a wide range of compounds, including known kinase inhibitors, possess this gain-of-function activity. These findings provide insights that might enable more rational design and optimization of molecular glue compounds.

    Research Briefing
  • Most miniature Cas12f nucleases have T-rich PAM specificity, restricting their targeting scopes. The cryo-EM structure of the Clostridium novyi Cas12f1 reveals the molecular basis for rare C-rich PAM recognition and enables optimization of sgRNA scaffold to improve CnCas12f1 activity.

    • Mengjiao Su
    • Fan Li
    • Quanjiang Ji
  • Detailed analysis of the structure–activity relationship for cyclin K degraders reveals diverse compounds that acquire glue activity through simultaneous binding to the CDK12 kinase pocket and engagement of several key DDB1 interfacial residues.

    • Zuzanna Kozicka
    • Dakota J. Suchyta
    • Nicolas H. Thomä
    ArticleOpen Access
  • Newly developed synthetic antibodies offer the means to be used as high-affinity, conformation-specific probes to capture dynamic repertoires of neddylated cullin–RING E3 ligase complexes. This allows nonenzymatic profiling of the diverse signaling networks that are based on these active complexes.

    • Aasna L. Parui
    • Helen Walden
    News & Views
  • Peptide phage display reveals a non-catalytic binding site on the intervening domain of O-GlcNAc transferase. Its roles in substrate recognition, posttranslational modification (PTM) crosstalk and nutrient response provide insight into the function of this cryptic domain.

    • Connor M. Blankenship
    • Jinshan Xie
    • Jiaoyang Jiang
  • By solving the cryogenic electron microscopy structures of bacterial calcium-activated potassium channels, Fan et al. report a pathway for blockers to enter the closed pore of the channels through membrane portals rather than through the canonical ion entryway, opening new avenues for drug-targeting this class of channels.

    • Chen Fan
    • Emelie Flood
    • Crina M. Nimigean
  • Tryptophan hydroxylases have only been known from eukaryotes and are involved in the biosynthesis of serotonin or melatonin. Here, the authors characterize a family of bacterial tryptophan hydroxylases that differ markedly from their eukaryotic counterpart in cofactor and catalytic mechanism.

    • Xinjie Shi
    • Guiyun Zhao
    • Yi-Ling Du
  • Since its proposition in 2002, the Division of Chemical Biology in the Department of Chemical Sciences at the National Natural Science Foundation of China has implemented a range of constructive initiatives to break down traditional boundaries between chemistry and biology and to further bridge these two fields, in order to boost the development of chemical biology in China.

    • Zhiyi Yu
    • Peng R. Chen
    • Yan Zhang
  • Homologous to E6AP C-terminus (HECT) E3s forge polyubiquitin chains through multiple reaction steps. A HECT polyubiquitylation cascade was visualized step-by-step, through use of chemical tools and cryo‐EM, and revealed how K48 linkage-specificity is attained by oligomeric UBR5.

    • Laura A. Hehl
    • Daniel Horn-Ghetko
    • Brenda A. Schulman
    ArticleOpen Access