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Using combined methods of modern chemical protein synthesis and structural biology, Ai et al. found a crosstalk mechanism of histone modifications, by which H2BK34ub stimulates the activity of the H3K79 methyltransferase Dot1L through inducing nucleosome distortion.
Antigen loading onto class I major histocompatibility complex (MHC-I) proteins relies on chaperones and protein flexibility. Researchers now provide new insight into the process, especially for the intriguing ‘non-classical’ MHC-I protein MR1, with implications for fundamental immunology and the development of novel immunotherapies.
Biochemical and structural approaches define how the chaperone TAPBPR interacts with MR1 molecules, including empty and ligand-loaded MR1, and facilitates presentation of metabolite-derived antigen ligands by MR1 complexes.
Carbon dioxide (CO2) is a product of cellular respiration that can also serve as a post-translational modification (PTM) through covalent protein modification. A new chemoproteomic strategy enables the capture of functional CO2-dependent carboxylation on lysine residues of proteins.
Comprehensive structural biology analysis of seven members of the S1 carbohydrate sulfatase family derived from human gut microbiome Bacteroides reveals mechanisms of glycan recognition and sulfate hydrolysis.
B-cell activation reprograms the TCA cycle and reduces cellular fumarate levels. Increased fumarate caused by fumarase inhibition or dimethyl-fumarate treatment directly succinates and inhibits LYN, leading to impaired B-cell activation and function.
Using isocyanic acid as a CO2 analog generates a stable mimic of lysine carboxylation, enabling development of a quantitative chemoproteomic approach to identify this modification in proteins and explore the lysine carboxylome of a cyanobacterium.
MNK2 was identified as the target of a small molecule named CID661578 that can stimulate pancreatic β-cell generation in zebrafish, pig and human organoids. CID661578 prevents MNK2 from binding to eIF4G in the translation initiation complex.
The zinc-sensor protein Zur in a marine cyanobacterium is distinct from those in other bacteria in structure and location of its sensory zinc site, and facilitates growth across a range of zinc concentrations via activation of a metallothionein gene.
Using nanobodies labeled with FRET fluorophores, the authors show the presence and activation of GPCR mGlu2 and mGlu4 dimers in mouse brain samples and reveal that mGlu2–mGlu4 is the major form of mGlu4-containing dimers outside the cerebellum.
The first crystal structure of human TMPRSS2, a proteolytic driver of SARS-CoV-2 infection in airways and an antiviral target, reveals structural features of viral spike protein and protease inhibitor binding.
The rising threat of antifungal resistance means that alternative therapeutics need to be considered. New research explores the biochemical basis of virulence inhibition by mucus glycans against the fungal pathogen Candida albicans.
Glycomic profiling of mucosal surfaces identified O-mucin glycoconjugate motifs that regulate Candida albicans virulence. Synthetic analogs based on these glycans suppress fungal filamentation, offering potential for antifungal development.
A fungal ten-eleven translocation (TET) dioxygenase homolog, CcTet, is found to have both 5-methylcytosine (5mC) and N6-methyladenine (6mA) demethylase activity. Structure-based engineering of CcTet yielded a 6mA-specific demethylase, offering a useful tool for the manipulation and functional study of 6mA.
A fungal dioxygenase CcTet displays robust demethylation activity against both N6-methyladenosine (6mA) and 5-methylcytosine on duplex DNA, while its D337F mutant exhibits specific activity against 6mA, providing a useful tool for 6mA functional study.
A redesigned antiviral miniprotein based on a dimeric helix-hairpin motif binds and dimerizes the RBD of the SARS-CoV-2 spike protein and inhibits viral infection by inhibiting spike interaction with ACE2.
A new targeting modality-based transcellular labeling technology called photocatalytic cell tagging enables monitoring of cell–cell interactions when combined with multiomics single-cell sequencing.
A DNA recording method based on an enhanced dCas12a base editor system enables the parallel and scalable recording of cellular signaling events in multiple mammalian cell types.
LRP8 regulation of cellular selenium promotes ferroptosis resistance in cancer. Low selenium leads to ribosome stalling, ribosome collisions and early GPX4 translation termination.
