NMR provides a useful tool in the study of protein dynamics and the mechanisms behind protein function and malfunction in pathological states. This research area has been of particular interest to Professor Arthur Palmer, Director of NMR Spectroscopy at the New York Structural Biology Center and Professor of Biochemistry and Molecular Biophysics at Columbia University. For the past 22 years, Palmer’s research has focused on the use of NMR to study relaxation in proteins and other macromolecules. Currently, his research is looking at areas such as protein folding, molecular recognition by proteins and enzyme catalysis.
In a recent interview, Palmer talked through two recent examples of how NMR spin relaxation is such a powerful technique for applying to biological problems in the study of protein dynamics and chemical kinetic processes.
In one study, Palmer and colleague, Dr Ying Li, used NMR spin relaxation to demonstrate an important mechanism underlying the dimerization of E-cadherin, a key cell adhesion molecule. The research showed that an X-dimer was essential to the dimerization process and for setting the time scale for the function of E-cadherin.
In another study, Palmer together with Dr Michelle Gill and colleagues, used a combination of NMR spin relaxation and fluorescence techniques to study the enzymatic mechanism of the DNA repair enzyme AlkB. They revealed a set of conformational changes in the dynamics of AlkB that control the pathway this protein follows in order to function.
“Both of these projects illustrate the power of NMR spectroscopy in probing dynamic properties and proteins which we believe underline most of their functions,” says Palmer.
One major focus of Palmer’s work is researching new techniques for use in NMR spin relaxation, research that has been driven by access to state-of-the-art technology, magnets, probes and consoles that the scientists use for everything they do.
Now, many other researchers are using some of the techniques Palmer and his colleagues have developed, but as far as the team’s own applications are concerned, they believe the most important contribution has been demonstrating the importance of measuring protein dynamics and conformational disorder. They say such analysis can lead to an in-depth understanding of the mechanisms behind protein function and therefore malfunction, in disease and other pathological states.
Palmer expects that the increasingly higher magnetic field strengths that are being achieved as technology advances, will open up even more opportunities in the future, as the threshold extends to as high as 1 gigahertz and beyond. He also emphasises the importance of sensitivity. Invariably, the most key biological systems are the least stable ones with the lowest solubility and the more quickly high quality data can be obtained, the greater likelihood there will be of successfully probing these systems. The continued development of highly sensitive probes and receivers is therefore also crucial, says Palmer.