Researchers Reveal Insights Into A Protein Linked With Diabetes And Hypertension
The amount of water and salt in our cells and their pH are strictly monitored for cell survival. To establish the necessary balance, special proteins play the key role of exchanging protons for lithium or sodium ions across the cell membranes. These proteins are called sodium-proton exchangers.
Sodium-proton exchangers are present in every cell and regulate cell pH, sodium content and volume by transporting sodium into the cell in exchange for hydrogen. If these proteins do not function properly, it can lead to diseases such as diabetes, cancer, heart failure and hypertension.
NHA2 is an important NHE, a protein found in the membrane of kidney cells. It controls blood pressure and beta cells, which regulate blood glucose levels by secreting, storing and releasing insulin. The salt-absorbing NHA2 was recently discovered to be the long-sought sodium-proton exchanger associated with diabetes and hypertension in humans. However, despite its importance, very little is known about its structure and how it works.
The EU-funded EXCHANGE project investigated what NHA2 looks like and how it adapts to the membrane. The new insights into this important biological mechanism could lead to the development of new drugs against two diseases mentioned earlier. The findings are described in a paper published in Nature Structural & Molecular Biology.
To reach the results, the research team combined biochemistry, electrophysiology, molecular dynamics simulations, cryogenic electron microscopy and native mass spectroscopy. This led to the discovery of the structure of NHA2, according to a news release on the website of the EXCHANGE project coordinator at Stockholm University, Sweden.
The discovery also allowed the researchers to figure out how the protein rearranges itself to become more active in the presence of a particular lipid.
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