FAST FOLDING OF A PROTOTYPIC POLYPEPTIDE - THE IMMUNOGLOBULIN BINDINGDOMAIN OF STREPTOCOCCAL PROTEIN-G

The folding of the small (56 residues) highly stable B1 immunoglobulin binding domain (GB1) of streptococcal protein G has been investigated by quenched-flow deuterium-hydrogen exchange. This system represents a paradigm for the study of protein folding because it exhibits no com plicating features superimposed upon the intrinsic properties of the p olypeptide chain. Collapse to a semicompact state exhibiting partial o rder, reflected in protection factors for ND-NH exchange up to 10-fold higher than that expected for a random coil, occurs within the dead t ime (less than or equal to 1 ms) of the quenched flow apparatus. This is followed by the formation of the fully native state, as monitored b y the fractional proton occupancy of 26 backbone amide groups spread t hroughout the protein, in a single rapid concerted step with a half-li fe of 5.2 ms at 5 degrees C.