A NOVEL, HIGHLY STABLE FOLD OF THE IMMUNOGLOBULIN BINDING DOMAIN OF STREPTOCOCCAL PROTEIN-G

The high-resolution three-dimensional structure of a single immunoglobulin binding domain (BI, which comprises 56 residues including the NH2-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 (angstrom) for the backbone atoms, 0.65 angstrom for all atoms, and 0.39 angstrom for atoms excluding disordered surface side chains. The structure has no disulfide bridges and is composed of a four-stranded 13 sheet, on top of which lies a long helix. The central two strands (beta-1 and beta-4), comprising the NH2- and COOH-termini, are parallel, and the outer two strands (beta-2 and beta-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-degrees-C).