Solving large protein structures by NMR

Nuclear magnetic resonance (NMR) spectroscopy is useful for solving protein structures in solution, but spectral overlap becomes problematic with increasing protein size, preventing routine structure determination of larger proteins. Two papers address this challenge by presenting hybrid methods that couple sparse NMR information with alternative structural information in order to solve protein structures. Shen and Bax introduce an alignment approach that takes experimental NMR chemical shifts and matches them to chemical shift values predicted for crystal structures, thereby generating a structure template that is subjected to a modeling pipeline for structure determination. Montelione, Marks, Sander and colleagues describe a hybrid approach that combines sparse NMR chemical shift, nuclear Overhauser effect and residual dipolar coupling data with evolutionary residue-residue coupling information derived from sequence alignments to improve the accuracy of structures modeled from sequence information alone. Both groups demonstrate success in determining the structures of proteins larger than 40 kilodaltons. Brief Communications p747, p751