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.

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.

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.

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.

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.

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.

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.