Secretagogin is a Ca2+-dependent stress-responsive chaperone that may also play a role in aggregation-based proteinopathies

Secretagogin (SCGN) is a three-domain hexa-EF-hand Ca²⁺-binding protein that plays a regulatory role in the release of several hormones. SCGN is expressed largely in pancreatic β-cells, certain parts of the brain, and also in neuroendocrine tissues. The expression of SCGN is altered in several diseases, such as diabetes, cancers, and neurodegenerative disorders; however, the precise associations that closely link SCGN expression to such pathophysiologies are not known. In this work, we report that SCGN is an early responder to cellular stress, and SCGN expression is temporally upregulated by oxidative stress and heat shock. We show the overexpression of SCGN efficiently prevents cells from heat shock and oxidative damage. We further demonstrate that in the presence of Ca²⁺, SCGN efficiently prevents the aggregation of a broad range of model proteins in vitro. Small-angle X-ray scattering (BioSAXS) studies further reveal that Ca²⁺ induces the conversion of a closed compact apo-SCGN conformation into an open extended holo-SCGN conformation via multistate intermediates, consistent with the augmentation of chaperone activity of SCGN. Furthermore, isothermal titration calorimetry establishes that Ca²⁺ enables SCGN to bind α-synuclein and insulin, two target proteins of SCGN. Altogether, our data not only demonstrate that SCGN is a Ca²⁺-dependent generic molecular chaperone involved in protein homeostasis with broad substrate specificity but also elucidate the origin of its altered expression in several cancers. We describe a plausible mechanism of how perturbations in Ca²⁺ homeostasis and/or deregulated SCGN expression would hasten the process of protein misfolding, which is a feature of many aggregation-based proteinopathies.     

Design and Optimization of Novel ZnS–Metal Core-Shell Random Structures for Light Harvesting—a Computational Study

Plasmonics - We present a systematic computational study on the optical properties of a new composite structure based on ZnS–metal core-shell particles, which can find applications in light...     

3,4,7-Trimethylcoumarin from Trigonella foenum-graecum stems

A trimethylcoumarin has been isolated, for the first time from the stem of Trigonelia foenum-graecum along with some known compounds. Based upon spectral and analytical data and comparison with a synthetic sample, it has been assigned the structure 3, 4, 7-trimethylcoumarin.