A Novel, Highly Stable Fold of the Immunoglobulin Binding Domain of Streptococcal Protein G

• Published in: Science (American Association for the Advancement of Science) Vol. 253; no. 5020; pp. 657 - 661
• Main Authors: Gronenborn, Angela M., Filpula, David R., Essig, Nina Z., Achari, Aniruddha, Whitlow, Marc, Wingfield, Paul T., Clore, G. Marius
• Format: Journal Article
• Language: English
• Published: Washington, DC American Society for the Advancement of Science 09.08.1991; American Association for the Advancement of Science; The American Association for the Advancement of Science
• Subjects: Amino Acid Sequence; Atomic structure; Atoms; Bacterial Proteins - chemistry; Bacterial Proteins - immunology; Binding Sites; Biological and medical sciences; Calorimetry; Coordinate systems; Electronic structure; Fundamental and applied biological sciences. Psychology; G proteins; Geometric angles; Hydrogen Bonding; Hydrogen bonds; Immunoglobulin G; Immunoglobulins; Magnetic Resonance Spectroscopy - methods; Models, Molecular; Molecular biophysics; N.M.R; Nuclear magnetic resonance; Nuclear magnetic resonance spectroscopy; Protein Conformation; Protein folding; protein G; Proteins; Protons; Simulated annealing; Spectroscopy; Structure in molecular biology; Topology; Tridimensional structure; Streptococcaceae; Streptococcus; Domain structure; Refolding; Bacteria; Micrococcales; NMR spectrometry; Secondary structure; Spatial structure; G protein
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.1871600

The high-resolution three-dimensional structure of a single immunoglobulin binding domain (B1, which comprises 56 residues including the NH$_2$-terminal Met) of protein G from group G Streptococcus has been determined in solution by nuclear magnetic resonance spectroscopy on the basis of 1058 experimental restraints. The average atomic root-mean-square distribution about the mean coordinate positions is 0.27 angstrom ($\angst $) for the backbone atoms, 0.65 $\angst $ for all atoms, and 0.39 $\angst $ for atoms excluding disordered surface side chains. The structure has no disulfide bridges and is composed of a four-stranded β sheet, on top of which lies a long helix. The central two strands (β 1 and β 4), comprising the NH$_2$- and COOH-termini, are parallel, and the outer two strands (β 2 and β 3) are connected by the helix in a +3x crossover. This novel topology (-1, +3x, -1), coupled with an extensive hydrogen-bonding network and a tightly packed and buried hydrophobic core, is probably responsible for the extreme thermal stability of this small domain (reversible melting at 87°C).