UCLA researchers have determined the atomic structure and function of NBCn1, a transporter protein that plays a role in breast cancer cell survival. The study reveals how this protein helps cancer cells maintain a stable internal environment even under conditions that are harmful to normal cells.
NBCn1 is responsible for moving alkali ions into breast cancer cells, which helps them keep their internal pH at levels that support growth and resistance to stress. Using cryo-electron microscopy and computational modeling, the team found that NBCn1 uses an "elevator-like" motion to transport two sodium ions and one carbonate ion efficiently. This mechanism allows the protein to move about 15,000 ions per second.
The acidic environment around tumors is often due to low oxygen and high metabolic activity. While healthy cells cannot survive easily in such conditions, cancer cells use proteins like NBCn1 to adapt by controlling their internal chemistry. Although NBCn1 was already known as a plasma membrane transporter involved in pH regulation, its detailed structure and method of efficient ion transport had not been previously understood.
To address this gap, the UCLA scientists used cryo-electron microscopy to obtain the first atomic-level, three-dimensional image of human NBCn1. Computational models helped them analyze how the protein changes shape during operation and trace the movement of ions through it.
According to the research team, understanding NBCn1's structure offers opportunities for drug development aimed at blocking this transporter. By targeting NBCn1 specifically in cancer cells, future therapies could disrupt tumor survival mechanisms while sparing healthy tissue.
"By understanding the structure and function of NBCn1, the study provides a blueprint for designing drugs that could potentially block this transporter and disrupt the internal chemical balance that cancer cells depend on. Targeting this protein in cancer cells specifically could offer a precise way to weaken tumors while minimizing harm to normal tissue," stated the researchers.
