Doodling Science: Protein Folding Deconstructed

BPJ_109_1.c1.inddHow did you compose this image?

The image is intended to illustrate a complex scientific idea in a naive and somewhat fairytale-like manner in the form of a doodle. In the creative process of designing experiments, scientists often doodle their notes and ideas in similar simplistic form before taking their design to the next level.

The image was composed on-the-fly by a graphical artist (Hanne Grønne) and a 16 year old girl (Asta Andersen) while the work was orally described to them and it reflects their direct interpretations. Neither of them have any scientific background.

How does this image reflect your scientific research?

The image reflects the main experimental method and the background of the project, which focused on deciphering details of the folding mechanism of a protein called neuronal calcium sensor-1 (NCS-1). Our approach involves applying force to individual NCS-1 protein molecules. To do this, we attach DNA molecular handles to the protein, and the handles are subsequently attached to micrometer-sized beads that are trapped using optical laser tweezers. With this method we can pull a single protein molecule and unravel its three-dimensional structure, while monitoring in real-time its dimensions and the resulting tension. This allows us to determine important details regarding the folding mechanism of a protein molecule under various conditions. In this paper we study the effects of ions on the folding mechanism of NCS-1. The figure, therefore, shows DNA molecules attached to a protein (NCS-1) and stick-figures holding each DNA, representing the unique control we have over the fate of the individual protein molecule, where we essentially grab the protein by its ends and pull it apart. The protein is shown as a clover leaf with ions bound (shown as black circles) and there are references to a membrane (NCS-1 attaches to the membrane), forces (picoNewton and Kg), dimensions (nanometers shown on a ruler), a laser (used to both induce and measure forces), a neuron (NCS-1 is localized primarily in neurons), and ions (spheres throughout the image). The picture is also meant to convey the complexity of biology in simplistic terms.

Can you please provide a few real-world examples of your research?

Various ions act as messenger molecules in cells such as calcium, magnesium, zinc, and iron ions. Calcium-binding proteins are ubiquitous signaling proteins in cells and many, including NCS-1, also bind other ions, mostly magnesium. Therefore, at any given time in the cell, at least three states can be envisioned: The Ca2+-bound state, the Mg2+-bound state, and a free state (with no ions bound). For NCS-1 and its related family, not much is known about the effects of ions on their folding mechanism. Because conformational dynamics is a hallmark of signaling, understanding the folding energy landscape is important to rationalize the conformational response to different ions, which is the process  that relays signals throughout the cell.

How does your research apply to those who are not working in your specific field?

Our work is highly relevant for a broad cross-section of bio-scientists working in the field of calcium- binding proteins, protein folding and dynamics, and neuroscience, and our methodology brings together physics, chemistry, and biology. Our results may be generally applicable to the vast superfamily of proteins that have EF-hand-motifs. In addition, experimentally derived folding energy landscapes are rare as they are difficult to determine with traditional methods and so our work may aid in understanding the general principles of protein folding.

Do you have a website where our readers can view your recent research?

The website of the Structural Biology and NMR Laboratory (Dr. Kragelund):

The website of the optical tweezers Laboratory (Dr. Cecconi):

– Mohsin M. Naqvi, Pétur O. Heidarsson, Mariela R. Otazo, Alessandro Mossa, Birthe B. Kragelund, and Ciro Cecconi


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