Stockholm University and SciLifeLab research uncovers how glucose transporters achieve specificity, bridging a long-standing gap between structure and function in membrane biology. The study is published in Nature Structural & Molecular Biology.

Scientists located at Stockholm University and SciLifeLab, Stockholm, have uncovered a crucial missing link in how sugar transporters move nutrients into cells.

“Our study shows that these transport proteins rely on a previously uncharacterized intermediate state that functions much like the ‘transition state’ in enzyme catalysis. This is a discovery that reshapes our understanding of one of biology’s most fundamental processes”, says David Drew, professor of biochemistry, Department of Biochemistry and Biophysics, Stockholm University.

From moulds to mammals, glucose is a primary energy source for life. To be used by cells, glucose must first enter the cell by crossing the cell’s membrane, via specialized proteins known as GLUT transporters. While these proteins have long served as textbook examples for applying enzyme-like kinetics to membrane transport, scientists have struggled to reconcile structural snapshots of these transporters with how they actually function in real time.

The new research addresses this challenge by combining advanced spectroscopy, protein engineering, and molecular simulations to reveal how transport specificity is determined—not at the point of initial sugar binding, as previously assumed, but during a later, transient step in the transport cycle.

“Our results show that substrate specificity is governed by the ability of a sugar to stabilize a transition-like intermediate state during transport,” David Drew explains. “This shifts the focus away from initial binding and toward dynamic conformational changes that occur mid-transport.”

The discovery provides a conceptual breakthrough by aligning the function of membrane transporters with the well-established framework of enzyme catalysis, where transition states play a central role. It also offers a new lens through which to interpret structural data and could inform future efforts to design drugs targeting glucose transporters in diseases such as cancer and diabetes.

More about the study
The article “A two-step mechanism for sugar translocation” is published in Nature Structural & Molecular Biology. DOI: 10.1038/s41594-026-01784-w
The work was a collaboration between David Drew, Department of Biochemistry and Biophysics, and Göran Widmalm, Kemikum, that was funded by Cancerfoundation and more recently an ERC AdG “MEMSUGAR” to David Drew, located at SciLifeLab.