HMN 2026: What is the molecular lock that helps power life on Earth

A new study reveals the dynamics of photosynthesis at the cellular level. Led by co-authors Professor Barry Bruce and Associate Professor Rajan Lamichhane, both of the Department of Biochemistry and Cellular and Molecular Biology (BCMB) at the University of Tennessee, Knoxville, the team published its findings—”Single-molecule fluorescence and cross-linking reveal ligand-gated Toc34 oligomerization dynamics”—in the Biophysical Journal. The team included graduate student Sree Kavya Penneru, whom Bruce and Lamichhane co-mentor, and postdoctoral researcher Sriram Tiruvadi-Krishnan.

The study reflects a highly productive collaboration. Bruce has investigated the mechanisms of chloroplast biogenesis for more than three decades, and this work extends that research into a powerful new dimension by introducing single-molecule resolution to the problem, made possible through the involvement of Lamichhane, a world leader in single-molecule FRET methodology. His expertise and custom-built instrumentation at UT Knoxville enabled the sophisticated nature of these experiments, resulting in a major technical and conceptual advance that allows parts of chloroplast biogenesis to be studied in more detail than was previously possible.

“This is a unique collaboration that bridges disciplines,” said Bruce. “Lamichhane’s work on GTPases in GPCR systems—central to drug discovery—is now being applied to a different but equally important GTPase system that controls chloroplast function in plants. This shift allows us to use advanced single-molecule tools to study a process that is fundamental to how plants produce the food, fiber and fuel on which society depends.”

A closer look at Toc34

Researchers have previously characterized the structure of the chloroplast, the specialized organelles in plants and algae that are the primary site of photosynthesis. Chloroplasts need to import most of their proteins from outside the organelle, and the Toc34 receptor helps control this entry process. Toc34 works as a pair of identical proteins (a homodimer), which can be thought of as two parts of the same lock on a door. Together, this Toc34 pair helps recognize incoming proteins and decide when the “door” should open.

“The two halves of the lock communicate with each other and use a small energy molecule (GTP) to switch between different states,” said Bruce. “However, we still do not fully understand how this ‘double lock’ changes shape or activity to control protein import.”

Next steps for the receptor system

The team will extend its strategy to other membrane-bound systems in future studies, expanding its approach to build a more complete model of the dynamic and coordinated events that take place within the workings of photosynthesis.

“In the future, we plan to double the complexity of these experiments by moving beyond the Toc34 homodimer to examine the full two-receptor system involving both Toc34 and Toc159,” said Bruce. “By revealing how the Toc34 ‘lock’ opens and closes, this work creates an opportunity either to make protein import more efficient—supporting stronger plant growth—or to precisely ‘jam the lock,’ offering a plant-specific strategy for new herbicides.”

The content is provided for information purposes only.