In Seminar, Chemistry Alum Explores How Protein Movements Shape Their Function
RNase H plays an important role in cutting RNA when it forms hybrids with DNA. Arthur Palmer’s research shows that different versions of this enzyme, found in different organisms, move in slightly different ways, affecting how well they work.
March 18, 2025 I By David DeFusco
Arthur Palmer, who holds a Ph.D. in chemistry from UNC-Chapel Hill, discussed how proteins shift their shapes and why that matters for their function in a recent presentation, “Conformational Dynamics Govern Function in Ribonuclease H Enzymes and Cadherin Cell Adhesion Proteins,” as part of a Biochemistry & Biophysics seminar series.
Proteins aren’t rigid structures—they constantly shift and change shape, which is essential for them to work properly. Palmer, the Robert Wood Johnson, Jr. Professor of Biochemistry and Molecular Biophysics at Columbia University Irving Medical Center, studies these movements using nuclear magnetic resonance (NMR) spectroscopy, a technique that allows scientists to observe proteins in motion and molecular dynamics simulations, which use computers to model these motions. His research focuses on two types of proteins: ribonuclease H (RNase H), an enzyme that helps break down RNA, and cadherins, which help cells stick together.
RNase H plays an important role in cutting RNA when it forms hybrids with DNA. Palmer’s research shows that different versions of this enzyme, found in different organisms, move in slightly different ways, affecting how well they work. A key part of the enzyme, called the handle region, can shift between open and closed states, and this movement impacts how the enzyme binds to its target.
Palmer’s team discovered that a specific amino acid at position 88 of the enzyme determines how flexible this handle region is. Changing this amino acid can make the enzyme switch between a single-state and a two-state behavior, which affects how well it functions. Their research suggests that both fully open and intermediate states are necessary for the enzyme to work efficiently.
Cadherins are proteins that allow cells to attach to one another, which is crucial for tissue structure and communication. Palmer’s research has shown that cadherins do not stay in just one shape but move between different states to adjust how strongly they bind. This insight helps explain how cells can stick together firmly in some situations and loosen their grip in others, which is important for processes like tissue development and cancer metastasis.
Beyond studying specific proteins, Palmer has also improved the tools scientists use to study protein movements. His work in NMR spectroscopy has made it easier to measure protein shape changes accurately. He has also developed better methods for analyzing how proteins switch between different conformations, which is crucial for understanding their functions.
This knowledge could be used to design new medicines that target proteins more effectively. By understanding how proteins shift between different shapes, researchers might develop drugs that enhance or block these movements, leading to better treatments for diseases.
Palmer, who was elected last year to the National Academy of Sciences, will be inducted on April 25 in Washington, D.C. He said he’s “extremely proud” to have been Dr. Nancy Thompson’s first graduate student in 1985.
“The ways of thinking about protein biophysics I learned then have infused my career for the past 40 years,” he said. “I’ve been fortunate to have wonderful mentors, including Nancy and Peter Wright, my postdoctoral advisor, and simply fantastic graduate students, postdoctoral scientists and colleagues at Columbia.”