The amount of water and salt in our cells and their pH is strictly observed for cell survival. In order to strike the necessary balance, special protein perform the key role of exchanging protons for lithium or sodium ions across cell membranes. The proteins are termed sodium-proton exchangers.
Sodium-proton exchangers are present in every cell and they tightly regulate pH of cells, sodium levels and volume by moving sodium into the cell in exchange for hydrogen. When these proteins do not work properly, this may lead to diseases such as diabetes, cancer, heart failure, and hypertension.
Meanwhile, NHA2 is an NHE of note, which is a protein found in the membrane of kidney cells. It controls blood pressure and beta cells that regulate blood glucose levels by secreting, storing, and releasing insulin. The salt-absorbing NHA2 was recently discovered as the long desired sodium-proton exchanger associated with diabetes and hypertension in humans. Howbeit, despite its significance, very less is known about its structure and how it functions.
Research supported by EU-funded EXCHANGE project has determined how NHA2 looks like and how it adapts to the membrane. The new insight obtained on this significant biological mechanism could lead to the development of new drugs against two previously mentioned diseases. The findings are described in a paper published in the Nature Structural & Molecular Biology.
Importantly, to obtain results, the research team combined biochemistry, electrophysiology, molecular dynamics simulations, cryogenic electron microscopy, and native mass spectroscopy. This led to the discovery of NHA2’s structure as posted as a news item on the website of EXCHANGE project coordinator at Stockholm University, Sweden.
The discovery also enabled researchers to find how the protein reorders itself when a specific lipid is present in order to become more active.