Germline Genetic Variant Classification Requires More Equitable Reference Database Representation.

Germline genetic testing can aid diagnostic workups but may reveal variants of unknown significance (VUS). VUS do not provide definitive diagnoses and may worsen patient and family stress. VUS are more prevalent in populations that are underrepresented in large genomic databases.

Structures reveal opening of the store-operated calcium channel Orai.

The store-operated calcium (Ca) channel Orai governs Ca influx through the plasma membrane of many non-excitable cells in metazoans. The channel opens in response to the depletion of Ca stored in the endoplasmic reticulum (ER). Loss- and gain-of-function mutants of Orai cause disease.

Cyanylated Cysteine Reports Site-Specific Changes at Protein-Protein-Binding Interfaces Without Perturbation.

To investigate the cyanylated cysteine vibrational probe group's ability to report on binding-induced changes along a protein-protein interface, the probe group was incorporated at several sites in a peptide of the calmodulin (CaM)-binding domain of skeletal muscle myosin light chain kinase. Isothermal titration calorimetry was used to determine the binding thermodynamics between calmodulin and each peptide. For all probe positions, the binding affinity was nearly identical to that of the unlabeled peptide.