An Interesting Case of Vitamin D-Mediated Severe Hypercalcemia in a Patient With Renal Mass.

Hypercalcemia of malignancy (HCM) is the most common cause of hypercalcemia in hospitalized patients. The pathogenesis of HCM is often multifactorial. One of the rare causes of HCM is extra-renal production of 1,25-dihydroxyvitamin D (or calcitriol), which is often seen in patients with lymphoproliferative malignancies.

A deep learning method for predicting interactions for intrinsically disordered regions of proteins.

Intrinsically disordered proteins or regions (IDPs/IDRs) exist as ensembles of conformations in the monomeric state. Upon binding to a partner, they adopt various binding modes, ranging from becoming ordered upon binding, to binding in a multivalent manner, to remaining fuzzy in the bound state. Moreover, they can adopt different binding modes depending on the partner.

Multiscale simulations reveal architecture of NOTCH protein and ligand specific features.

NOTCH, a single-pass transmembrane protein, plays a crucial role in cell fate determination through cell-to-cell communication. It interacts with two canonical ligands, Delta-like (DLL) and Jagged (JAG), located on neighboring cells to regulate diverse cellular processes. Despite extensive studies on the functional roles of NOTCH and its ligands in cellular growth, the structural details of full-length NOTCH and its ligands remain poorly understood.

AlphaFold opens the doors to deorphanizing secreted proteins.

Danneskiold-Samsøe and coworkers have developed an in silico screening pipeline based on AlphaFold2 for identifying single-pass transmembrane receptors for secreted peptides that play important roles in cell-cell signaling. Their approach can be used to deorphanize a diverse range of ligands. The overall strategy can be valuable in screening for weak and transient interactions.