BBB seminar: Angela M. Gronenborn

Angela M. Gronenborn, Laboratory of Chemical Physics, NIDDK, National Institutes of Health, Bethesda, MD, USA (http://spin.niddk.nih.gov/amg/)

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. The observation of drastic changes in overall topology and quaternary structure caused by mutation of core residues in the small, highly stable and compact protein GB1 is an unusual finding and provides another example of the amazing versatility exhibited by proteins.

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 structure is a particularly intriguing example relating to the important problem of how oligomeric proteins can evolve from monomeric ones.