BBB seminar: Angela M. Gronenborn
The amazing versatility of proteins - structural polymorphism and evolution
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.
We are very pleased to welcome Dr. Angela Gronenborn back to Bergen to open this seminar series dedicated to the inauguration of the "Bygg for Biologiske Basalfag" (BBB). Angela Gronenborn is an internationally renowned specialist in macro-molecular structure determination using nuclear magnetic resonance (NMR) spectroscopy. In 1988, the first protein NMR structures appearing in the Protein Data Bank (PDB) came from her laboratory. Since then she and her research team have published more than 250 papers in this area, greatly contributing to our current understanding of cellular processes at the molecular and atomic levels.