Study: Peptides can form well-defined structures in harsh, Venus-like conditions

When exploring solar system bodies for signs of past or present life, scientists have mainly focused on planets that have (or had) a liquid surface similar to Earth’s. However, mounting evidence suggests that the ingredients for life may exist in a very different environment: the highly acidic clouds that blanket Venus.Those clouds are made up of about 98 percent sulfuric acid, which scientists had believed to be too acidic for complex biological molecules to survive. But in a new study, MIT researchers have shown that short peptides can not only remain stable in these extremely acidic conditions, they can also fold into shapes that may allow them to have biological functions.“If peptides find their way to that cloud layer of concentrated sulfuric acid, they will stay and be stably preserved in that cloud of droplets. And once these macromolecules have a defined three-dimensional structure, they can potentially have a function,” says Mei Hong, an MIT professor of chemistry and one of the senior authors of the new study.The findings suggest that scientists should not rule out planets that don’t resemble Earth in their search for life, says Sara Seager, the Class of 1941 Professor of Planetary Sciences in the Department of Earth, Atmospheric and Planetary Sciences and a professor in the departments of Physics and of Aeronautics and Astronautics.“We really don’t know the full extent of what planet archetypes are out there. We’re seeking exoplanets that might be a true Earth twin, but what if they’re all Venuses? Our findings definitely open up a whole range of possibilities,” says Seager, another senior author of the study. She will be joining the University of Toronto faculty in September.Janusz Petkowski, a research assistant professor at Wroclaw University of Science and Technology, is also a senior author of the paper, which appears this week in the Proceedings of the National Academy of Sciences. Jia Yi Zhang, an MIT graduate student, is the paper’s lead author, and former MIT postdoc Aurelio Dregni is also an author. Surviving harsh conditionsWhile Venus’s surface is too hot to be hospitable to life, its cloud layer, which extends from 30 to 40 miles above the planet’s surface, features milder temperatures suitable for life. The clouds are made from droplets of sulfuric acid, which can dissolve metals and destroys most biological molecules on Earth.Meteorites that contain peptide building blocks regularly enter Venus’s atmosphere, raising the possibility that those peptides could serve as building blocks for simple life forms — if they could survive the clouds’ corrosive environment.In 2020, Seager’s lab began a series of studies looking at whether different types of biological molecules could persist under those highly acidic conditions. In their initial experiments, working with MIT’s Department of Chemistry Instrumentation Facility (DCIF), they used nuclear magnetic resonance (NMR) spectroscopy — which measures the magnetic properties of atomic nuclei within molecules — to analyze the structures of a variety of molecules in a solution of nearly pure sulfuric acid. Those studies showed that nucleic acids, the building blocks of DNA, could remain intact under highly acidic conditions, as could lipids and amino acids. The next step was to figure out if peptides — short strings of amino acids — could persist, and more importantly, whether they could then fold into shapes that might give them biological functions.For that challenging task, researchers at DCIF suggested that Seager join forces with Hong, an NMR expert who has an advanced 800-megahertz solution NMR spectrometer in her lab. To their surprise, the researchers found that the peptides they studied remained stable for many weeks. They believe this is a result of the lack of water in such highly acidic solutions. At 98 percent sulfuric acid, there are very few water molecules, which means that hydrolysis, the chemical reaction that breaks peptide bonds in acid, can’t happen.“Without water, an acid that you would consider a harsh solvent suddenly is not as menacing as one might think,” Hong says.After confirming that the peptides remained intact, the researchers began to explore their structures. One of the peptides that the researchers analyzed, a molecule known as HHQ, is a synthetic seven-amino-acid peptide that Hong had previously studied for its role in forming catalytic amyloid fibrils. In water, this peptide forms flat beta sheets that eventually form long fibrils. However, in concentrated sulfuric acid, the researchers found that it takes on an entirely different shape — a loop shaped like the Greek letter omega. Such so-called omega loops are occasionally found in some naturally occurring proteins, where they form links between other structural motifs such as sheets or helices.The other two peptides that the researchers analyzed were a longer variation of HHQ, called HHQ13, and a completely different peptide called K7, which contains seven amino acids. These peptides also formed omega loops in sulfuric acid.The researchers believe that molecules of sulfuric acid act as a scaffold for the loops, sliding into the center of each loop and holding it in that shape. “What hadn’t been known is that peptides can survive so well and have specific three-dimensional shapes in an acidic environment,” Hong says.Structure and functionIn naturally occurring proteins in aqueous solution, omega loops are thought to play a role in protein folding and molecular recognition. Whether they could have other biological functions is not known. However, the fact that peptides can form well-defined, folded structures in acidic environments is an important step in showing that peptides may be able to perform biological functions in such environments.“Life needs to have specially shaped proteins so that they have a specific target they can latch onto and perform their function. Before this, people thought that peptides couldn’t survive in sulfuric acid, so showing peptides are not only stable, but also fold, is a really big deal,” says Seager, who is leading the Morning Star Missions to Venus.Adriaan Bax, chief of the Section on Biophysical NMR at the Laboratory of Chemical Physics at the National Institute of Diabetes and Digestive and Kidney Diseases, described the results as “important and unexpected.”“The observation that these peptides retain a substantial degree of conformational order in concentrated sulfuric acid raises the prospect that folded oligopeptide/protein structures can exist in such environments, potentially supporting the possibility of life in atmospheric conditions that are very different from Earth,” says Bax, who was not involved in the research.Seager now hopes to pursue additional studies of a molecule called peptide nucleic acid (PNA) — an artificially synthesized molecule that is similar to DNA but with the sugar-phosphate backbone replaced by a peptide backbone. Her lab has previously shown that this molecule, which doesn’t naturally exist on Earth but could offer a potential alternative to DNA, is stable as a single strand in highly acidic environments. She now hopes to study the stability of double-stranded PNA.The researchers also hope to analyze longer peptides to see if they also take on omega loop shapes, or other structures, in highly concentrated sulfuric acid.The research was funded by the Alfred P. Sloan Foundation, the NOMIS Foundation, and the National Institutes of Health.