Structures of Larger Proteins in Solution: Three- and Four-Dimensional Heteronuclear NMR Spectroscopy

• Published in: Science (American Association for the Advancement of Science) Vol. 252; no. 5011; pp. 1390 - 1399
• Main Authors: Clore, G. Marius, Gronenborn, Angela M.
• Format: Journal Article
• Language: English
• Published: Washington, DC American Society for the Advancement of Science 07-06-1991; American Association for the Advancement of Science; The American Association for the Advancement of Science
• Subjects: Atomic structure; Atoms; Biochemistry; Biological and medical sciences; Chemical equilibrium; Coordinate systems; Electronic structure; Fundamental and applied biological sciences. Psychology; Interleukin-1 - chemistry; Magnetic Resonance Spectroscopy; Magnetization; Models, Molecular; Molecular biophysics; Molecular Structure; Nuclear magnetic resonance; Nuclear magnetic resonance spectroscopy; Protein structure; Proteins; Proteins - chemistry; Protons; Solutions; Spectral resolution; Spectroscopy; Spectroscopy : techniques and spectras; Structure; Proteins; Investigation method; Molecular structure; Overhauser effect; NMR spectrometry; Review; N dimensional spectrometry; Spatial structure; Pulse sequence
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.2047852

Three- and four-dimensional heteronuclear nuclear magnetic resonance (NM_R) spectroscopy offers dramatic improvements in spectral resolution by spreading throughbond and through-space correlations in three and four orthogonal frequency axes. Simultaneously, large beteronuclear couplings are exploited to circumvent problems due to the larger linewidths that are associated with increasing molecular weight. These novel experiments have been designed to extend the application of NMR as a method for determining three-dimensional structures of proteins in solution beyond the limits of conventional two-dimensional NMR (∼100 residues) to molecules in the 150- to 300-residue range. This potential has recently been confirmed with the determination of the highresolution NMR structure of a protein greater than 150 residues, namely, interleukin-1β.