Chemists have provided a new perspective on how collagen found in dinosaur bones has managed to endure for millions of years: An interaction at the atomic level stops its bonds from being broken down by water.
Collagen, a protein that exists in bones and connective tissue, has been discovered in dinosaur fossils dating back as far as 195 million years. This greatly surpasses the standard half-life of peptide bonds that connect proteins, which is approximately 500 years.
A recent study from MIT explains how collagen can last much longer than anticipated. The research team discovered that a distinctive atomic-level interaction protects collagen from being damaged by water molecules. This protective barrier inhibits water from disrupting the peptide bonds through a process called hydrolysis.
“We provide evidence that this interaction prevents water from attacking the peptide bonds and breaking them apart. This goes against the expected behavior of a typical peptide bond, which only lasts about 500 years,” explains Ron Raines, the Firmenich Professor of Chemistry at MIT.
Raines is the senior author of the new study, which will be published in ACS Central Science. MIT postdoc Jinyi Yang PhD ’24 is the lead author of the paper, with contributions from postdoc Volga Kojasoy and graduate student Gerard Porter.
Water-resistant
Collagen is the most prevalent protein in animals and is present not just in bones, but also in skin, muscles, and ligaments. It consists of long protein strands that twist together to create a robust triple helix structure.
“Collagen serves as the framework holding us together,” Raines states. “Its stability and suitability for this framework stem from its fibrous nature, which is different from most proteins.”
In the last ten years, paleobiologists have discovered collagen preserved in dinosaur fossils, including an 80-million-year-old Tyrannosaurus rex fossil and a sauropodomorph fossil nearly 200 million years old.
For over 25 years, Raines’ lab has investigated collagen to understand how its structure supports its function. In this new study, they highlighted why the peptide bonds in collagen are so resistant to breakdown by water.
Peptide bonds form between a carbon atom from one amino acid and a nitrogen atom of the next amino acid. The carbon atom also creates a double bond with an oxygen atom, resulting in a structure known as a carbonyl group. This carbonyl oxygen contains a pair of electrons not bonded to any other atoms. The researchers discovered that these electrons can be shared with the carbonyl group of an adjacent peptide bond.
This electron sharing prevents water molecules from infiltrating the bond structure and causing disruption.
To demonstrate this concept, Raines and his team developed two versions of collagen that can switch forms—one that typically forms a triple helix (the trans form) and another with rotated peptide bond angles (the cis form). They found that the trans version of collagen effectively kept water from hydrolyzing the bond. In contrast, the cis variant allowed water to penetrate, leading to bond breakage.
“Every peptide bond is either in cis or trans form, and we can adjust the ratio between the two. This allows us to simulate the natural condition of collagen or generate an unprotected peptide bond, which we found deteriorated quickly when unprotected,” Raines states.
“No weak link”
This electron-sharing phenomenon has also been observed in protein structures known as alpha helices, found in various proteins. Although these helices might also be shielded from water, they are always connected by more exposed protein sequences vulnerable to hydrolysis.
“Collagen consists entirely of triple helices throughout its structure,” Raines notes. “There are no weak links, which I believe contributes to its longevity.”
Previously, some researchers suggested alternative explanations for collagen’s preservation over millions of years, including the idea that the bones were so dehydrated that water couldn’t reach the peptide bonds.
“While I can acknowledge the role of other factors, 200 million years is a significant duration, and I think a molecular or atomic-level explanation is necessary to account for it,” Raines comments.
The research was sponsored by the National Institutes of Health and the National Science Foundation.
