On-demand unfolding

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On-demand unfolding

We love engineering DNA here, and we also have a passion for proteins. So what could be better than combining them? Let’s dive into today’s paper then!

Inside cells, chemical reactions often happen in separate compartments. This setup has a few advantages: it reduces problems with toxic pathway intermediates, keeps competing metabolic reactions separate, and helps when enzymes have slow turnover rates (looking at you, RuBisCO). Researchers have developed different flavors of synthetic compartments, using lipid, protein or DNA-based scaffolds, both in cellular and in cell-free systems.

Today’s article introduces a DNA origami-based nanocompartment system designed to control and enhance the activity of two enzymes. The system features two adjacent compartments, each designed to host one enzyme and to optimize their respective reactions.

• The first compartment houses p97, a protein unfolding machine involved in cell homeostasis, proliferation and signalling.

• The second compartment hosts α-chymotrypsin, an enzyme that breaks down proteins once unfolded.

This setup creates a highly controlled environment where reactions are confined and optimized, minimizing unwanted interactions and maximizing reaction rates. The team reports a tenfold increase in the efficiency of protein degradation compared to the non-compartmentalized systems, with non-specific proteolysis down by around six-fold. Plus, the system is modular: different enzymes can be inserted into the compartments to create custom biochemical pathways.

This paper showcases one of the coolest ways to combine DNA and proteins: using DNA for precise positioning and proteins for functionality. These nanocompartments could be used to create synthetic nanofactories, creating new biochemical pathways, or to selectively modify molecules, such as DNA or proteins.

So, go read the paper for yourself here!

In other news:

• Jurassic Park, but with more DNA: Someone once said that life imitates art. This paper seems to confirm it: the team developed a new method to store DNA in deconstructable glassy polymer networks, inspired by how amber can preserve biological specimens over millennia. The new method offers an efficient, low-cost solution for long-term nucleic acid storage: plus, it’s called T-REX. You don’t need more to convince me.

• Loading DNA: Cells interact with the extracellular matrix (ECM) through integrin receptors: these interactions involve tiny forces, but the dynamics, especially force loading rates, are not well understood. This study introduces a new DNA-based probe that detects two force thresholds (4.7 pN and 47 pN) through distinct fluorescent signals in live cells. It showed that integrin bonds over 4.7 pN last about 45.6 seconds, with some forces increasing to over 47 pN at 1.1 pN per second, mostly at the cell's edge. This modular probe can be adapted to study other proteins or cells.

• Of amber and bears: Talking about animals preserved in amber. In this study researchers reanalyzed fossils of tardigrades, also called water bears. They look like microscopic sausages with legs, but they can survive the harshest environments, including outer space. Using laser confocal microscopy, the team studied the 3D structures of details of the two 80 million years old fossils, and to determine the species of one of the specimens, until now unknown. Fun fact: apparently, there are only three accepted tardigrades fossils in total.

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