Dr Angela Gronenborn
National Institutes of Health
Bethesda, MD

Thursday, September 18, 2003
12:00 am (CT)
3169 Beckman Institute

Abstract

Structures of hydrophobic core residue mutants of the immunoglobulin binding domain B1 of streptococcal protein G (GB1), a universal model protein, were determined. Surprisingly, the oligomeric state and quaternary structure of several of these mutant proteins is drastically changed. A domain-swapped dimer and a symmetric tetramer, with inter-molecular strand-exchange involving all four units were found. Our results demonstrate that through the acquisition of moderate numbers of point mutations proteins are able to undergo substantial global rearrangements and the loss of stability of the monomeric unit can be compensated for by multimerization. The current structures are particularly intriguing example relating to the important problem of how oligomeric proteins can evolve from monomeric ones and provides another example of the amazing versatility exhibited by proteins.