Assistant Professor Jian Hu highlighted in journal
- Jun 3, 2016
- Jian Hu
Biochemistry & Molecular Biology and Chemistry Assistant Professor Jian Hu was part of a team that’s providing new insights into the molecular basis of human diseases resulting from mutations in the calcium-sensing receptor, or CaSR, a protein found in cell membranes. CaSR plays a crucial role in maintaining calcium concentration in the human body. However, the molecular basis underlying how CaSR regulates such important cell function has been unclear.
The team’s findings, published in the 27 May 2016 issue of Science Advances, may assist in the development of novel receptor-based therapeutics for mutations that lead to certain types of hypocalcemia and neonatal hyperparathyroidism, in addition to Alzheimer’s disease and some cancers. They reported the first crystal structure of the extracellular domain of the human CaSR, which enables them to visualize a large number of residues involved in disease-associated mutations.
They detected an unexpected tryptophan derivative bound in the hinge region between two globular subdomains of the receptor protein. The discovery could lead to receptor-based therapeutics for use in the treatment of many different diseases.
“It is quite interesting that an unexpected small molecule occupies the native ligand binding site and functions as a high-affinity co-activator, which suggests that it may serve as a lead compound for CaSR regulators,” said Professor Hu. Their discoveries lay the groundwork for the development of agonists and antagonists as potential therapies for human diseases related to the CaSR.
Additional researchers from Georgia State and Brigham and Women's Hospital contributed to this study, which was supported by the National Institutes of Health and the Georgia Research Alliance.
The full article can be seen on MSU Today.