Structural Elements of Dwarf Open Reading Frame Required for Activation of the Sarco-Endoplasmic Reticulum Calcium Pump.

The sarco-endoplasmic reticulum calcium pump (SERCA) is a P-type ATPase that plays a critical role in intracellular calcium signaling. SERCA maintains the calcium gradient between the cytosol and the sarco-endoplasmic reticulum, which is essential for a variety of physiological events including the muscle contraction-relaxation cycle. In cardiac muscle, SERCA is regulated by transmembrane peptides phospholamban (PLN) and dwarf open reading frame (DWORF).

Structural insights into the nirmatrelvir-resistant SARS-CoV-2 M L50F/E166A/L167F triple mutant-inhibitor-complex reveal strategies for next generation coronaviral inhibitor design.

Drug-resistance is an eminent threat in antiviral therapy, and is currently a concern in nirmatrelvir-based therapy of SARS-CoV-2. Nirmatrelvir (antiviral component in Paxlovid) binds covalently to the active site cysteine of the main protease of SARS-CoV-2 (M), thereby blocking enzyme activity and halting viral replication. passage experiments mimicking a multi-dosage nirmatrelvir treatment regime, identified M variants with mutations in the active site and near the C-terminal dimerization interface with variable levels of nirmatrelvir resistance.

Cofactor-Independent Amino Acid Epimerases with Catalytic Serines Instead of Cysteines.

D-amino acids play important roles in nature and are often produced from their L-stereoisomers by racemase or epimerase enzymes. One interesting class of amino acid racemases and epimerases are the cofactor-independent enzymes, which rely on a pair of active site cysteine residues for catalysis in an unusual chemical mechanism with seemingly mismatched acidity values. One classic example of these enzymes is diaminopimelic acid epimerase (DapF-CC), which produces D,L-diaminopimelic acid (DAP) as the penultimate step in lysine biosynthesis in most bacteria and photosynthetic organisms, and for Gram-negative bacterial peptidoglycan.

Separable dorsal raphe dopamine projections mimic the facets of a loneliness-like state.

Affiliative social connections facilitate well-being and survival in numerous species. Engaging in social interactions requires positive or negative motivational drive, elicited through coordinated activity across neural circuits. However, the identity, interconnectivity, and functional encoding of social information within these circuits remains poorly understood.

Structural and genetic determinants of zebrafish functional brain networks.

Network science has revealed universal brain connectivity principles across species. However, several macroscopic network features established in human neuroimaging studies remain underexplored at cellular scales in small animal models. Here, we use whole-brain calcium imaging in larval zebrafish to investigate the structural and genetic basis of functional brain networks.