Coenzyme A (CoA) is an essential metabolic cofactor whose biosynthesis is controlled by pantothenate kinases (PANKs), the rate-limiting enzymes in CoA synthesis. Although CoA production is extensively...

The PLANT CYSTEINE OXIDASE (PCO) N-degron pathway contributes to oxygen sensing in plants. Here the authors identify HYPOXIA TRANSDUCER1 (HYT1) as a substrate of PCO and show it forms a coherent feed-...

The PLANT CYSTEINE OXIDASE (PCO) N-degron pathway contributes to oxygen sensing in plants. Here the authors identify HYPOXIA TRANSDUCER1 (HYT1) as a substrate of PCO and show it forms a coherent feed-...

To explore how cohesin organizes chromatin domains in living human cells, we combined single-nucleosome imaging/tracking5,29,44,45,54 with rapid cohesin depletion using the auxin-inducible degron (AID2) system55. Single-nucleosome imaging/tracking can sensitively detect changes in the chromatin state in living cells. We used HCT116 cells expressing H2B-HaloTag (H2B-Halo)45 and RAD21-mAID-mClover (mAC55; Extended Data Fig. 1a,b). H2B-Halo was labeled with tetramethylrhodamine (TMR) to visualize nucleosomes genome wide, including those in both euchromatin and heterochromatin (Extended Data Fig. 1c). Oblique illumination (highly inclined and laminated optical sheet, HILO) microscopy56 enabled imaging of individual nucleosomes as TMR-labeled dots of H2B-Halo (Fig. 1a–c), which were precisely tracked in two-dimensional (2D) at 50 ms per frame for a total of 15–20 s, yielding ~1,400 trajectories per cell (Fig. 1b,d and Extended Data Fig. 1d,e; see Methods for further details). Position-determination accuracy is 12.5 nm (Extended Data Fig. 1d). Tracking was specific to nucleosome-incorporated H2B-Halo, as the small free H2B-Halo pool (3.3%) diffused too fast to be observed (Supplementary Video 1 and Extended Data Fig. 1f). The mean squared displacement (MSD) analysis revealed subdiffusive nucleosome motion with an anomalous exponent (α) of 0.43, suggesting constrained motion (Fig. 1e,g, black plots). Fixation nearly abolished this motion (gray plot, Fig. 1e,g)...

Abstract. Recent discoveries have fundamentally transformed the paradigm of plant oxygen sensing. Hypoxia is no longer viewed solely because of environment

Abstract. Recent discoveries have fundamentally transformed the paradigm of plant oxygen sensing. Hypoxia is no longer viewed solely because of environment

Abstract. Recent discoveries have fundamentally transformed the paradigm of plant oxygen sensing. Hypoxia is no longer viewed solely because of environment

Deubiquitylases are key proteolytic regulators of ubiquitin-dependent cellular processes, catalyzing the removal or remodelling of ubiquitin modifications on substrate proteins, including those target...

Deubiquitylases are key proteolytic regulators of ubiquitin-dependent cellular processes, catalyzing the removal or remodelling of ubiquitin modifications on substrate proteins, including those target...

Liu et al. define how the CRL2ZYG11B ubiquitin ligase assembles and recognizes Gly/N-degron substrates by cryo-EM. Structures with an NLRP1 Gly/N-degron and SARS-CoV-2 ORF10 reveal extended substrate-binding surfaces besides the Gly-binding pocket, explaining N-degron selectivity and suggesting how viral mimicry can suppress inflammasome activation.

Intrinsically disordered regions (IDRs) of proteins are thought to be inherently sensitive to proteolysis and considered one of the key components constituting an efficient degron. Here we report that IDRs can also suppress protein degradation. Our recent study showed that yeast ribosomal proteins, while posttranslationally stable, are subject to cotranslational protein degradation (CTPD). In mapping the degron responsible for CTPD of ribosomal protein Rpl8A, we found that its N-terminal IDR suppresses CTPD, whereas the adjacent structured domain acts as a degron. We further assessed the N-terminal IDRs of 9 other yeast proteins and found that they all inhibit CTPD. These results suggest that suppression of CTPD is likely a generic function of N-terminal IDRs. Moreover, we showed that the N-terminal IDR of human ribosomal protein hRpl7A also functions as a stabilizer against CTPD in human cells. When transplanted to the N-terminus of cystic fibrosis transmembrane conductance regulator (CFTR), the N-terminal IDR of hRpl7A reduces CTPD of CFTR by more than 80%. Thus, the stabilizer function of N-terminal IDRs is conserved from yeast to human. Using mass spectrometry, we demonstrated that HSP70 chaperone proteins Ssa and Ssb bind to the N-terminal IDR of Rpl8A. These data suggest that N-terminal IDRs may inhibit CTPD through recruiting HSP70 chaperone proteins to nascent chains, thereby facilitating cotranslational folding. Our study unveils a new role for IDRs in suppressing CTPD.

Liu et al. define how the CRL2ZYG11B ubiquitin ligase assembles and recognizes Gly/N-degron substrates by cryo-EM. Structures with an NLRP1 Gly/N-degron and SARS-CoV-2 ORF10 reveal extended substrate-...

Read the full paper: Structure of the E3 ligase CRL2ZYG11B with substrates reveals the molecular basis for N-degron recognition and ubiquitination