Spying On Fleeting Proteins

Science

STRUCTURALLY DISTINCT The fleeting folding intermediate of an FF domain (left) differs substantially from that of the fully folded version (right).

Protein intermediates—fleeting structures that are here one millisecond and gone the next—are very difficult to observe. But a way to visualize some of them has been found by Lewis E. Kay of the University of Toronto; Alan R. Fersht of the Medical Research Council Centre for Protein Engineering, in Cambridge, England; and coworkers. The technique combines nuclear magnetic resonance relaxation dispersion spectroscopy with CS-Rosetta, a chemical-shift-based method for structure elucidation. The researchers demonstrated the approach by using it to structurally analyze, at atomic resolution, an intermediate on the folding pathway of an FF domain, a common protein motif. However, the method “is not restricted to folding intermediates but ­includes excited states important for function—for example, enzyme catalysis and ligand binding,” they write in Science (2010, 329, 1312). In an accompanying commentary, Hashim M. Al-Hashimi of the University of Michigan notes that the study ushers in “a new era in which researchers can determine the high-resolution structure of the excited states of proteins. … It seems inevitable that the entire protein structure landscape will soon succumb to NMR and computation.”

Chemical & Engineering News

ISSN 0009-2347

Copyright © 2011 American Chemical Society