Mercury is an exceptionally toxic element, but its danger escalates significantly when it is converted into methylmercury – a form so perilous that mere billionths of a gram can inflict severe and enduring neurological damage to a developing fetus. Alarmingly, methylmercury frequently enters our bodies through seafood, and once it contaminates our food and environments, eliminating it is quite challenging.
Recent research conducted at the Stanford Synchrotron Radiation Lightsource (SSRL) at the U.S. Department of Energy’s SLAC National Accelerator Laboratory has uncovered a surprising key factor in methylmercury poisoning – a molecule known as S-adenosyl-L-methionine (SAM). These findings hold promise for researchers seeking innovative strategies to combat methylmercury poisoning.
“Nobody knew how mercury is methylated biologically,” said Riti Sarangi, a senior scientist in SSRL’s Structural Molecular Biology program and co-author of the paper. “We need to understand that fundamental process before we can develop an effective methylmercury remediation strategy. This study is a step toward that.”
The new research focuses on a specific but crucial enigma regarding the production of methylmercury. Scientists have established that most of the mercury we ingest originates from industrial emissions that enter aquatic systems, where microorganisms convert it into methylmercury. This form accumulates in fish – and ultimately in humans – as it ascends the food chain.
Despite this understanding, scientists have struggled to pinpoint how these microorganisms actually create methylmercury. A significant challenge, as noted by researcher Sarangi, is that the key protein system responsible for this conversion, known as HgcAB, exists in exceedingly small quantities within microbes. This scarcity complicates efforts to collect and purify enough of the protein for study. Additionally, it is remarkably sensitive; even minor exposure to oxygen and light can render HgcAB inactive.
After a decade-long effort involving collaborations among national laboratories and universities, University of Michigan professor Steve Ragsdale, his former graduate student Katherine Rush, who is now an assistant professor at Auburn University, and postdoctoral associate Kaiyuan Zheng created a new protocol that produces enough stable HgcAB to finally explore how it converts mercury into methylmercury.
“We’ve worked with a lot of very difficult proteins, but this one had everything you would not want to have in a protein if you wanted to purify it. It was very complicated,” Ragsdale said.
After successfully purifying sufficient HgcAB, the team transported the samples—cooled with liquid nitrogen and shielded from light— to SSRL for crucial X-ray absorption spectroscopy measurements. At SSRL, associate scientist Macon Abernathy employed extended X-ray absorption fine structure spectroscopy to delve into the properties of HgcAB.
“SSRL’s X-ray spectroscopy facilities are especially equipped to study biological samples and have powerful detector systems that can resolve the extremely weak signals of ultra dilute protein samples like these,” Sarangi said.
While earlier studies speculated that the methyl group originated from methyltetrahydrofolate, a prevalent methyl donor in cellular processes, the new investigation decisively reveals that SAM is the true donor. The researchers assert that these findings clarify the key players in methylmercury production, which could significantly enhance the development of effective environmental remediation strategies.
“No one has tried it yet, but perhaps analogs of SAM could be developed that could address methylmercury in the environment,” Ragsdale said.
Journal reference:
- Kaiyuan Zheng, Katherine W. Rush, Angela S. Fleischhacker, Macon J. Abernathy, Ritimukta Sarangi, and Stephen W. Ragsdale. S-adenosyl-L-methionine is the unexpected methyl donor for the methylation of mercury by the membrane-associated HgcAB complex. Proceedings of the National Academy of Sciences, 2024; DOI: 10.1073/pnas.2408086121
