ONE-STEP EVOLUTION OF A DIMER FROM A MONOMERIC PROTEIN

Deletion of six amino acids in a surface loop transforms staphylococca l nuclease from a monomeric protein into a very stable dimer (K-d<1X10 (-8) M). A 2 Angstrom X-ray crystal structure of the dimer (R=0.176) s hows that the carboxy-terminal alpha-helix has been stripped from its normal position in one monomer and is now incorporated into the equiva lent position on the adjoining monomer. This swapping creates an assoc iation interface of 2900 Angstrom(2). A second, smaller interface of 4 60 Angstrom(2) is also formed. The spontaneous exchange or swapping of secondary structural elements provides a simple pathway for the forma tion of large, stable protein/protein interfaces and may play an impor tant role in the evolution of oligomeric proteins.