• Calendar

February 21, Tuesday
12:00 – 13:00

All living cells use very large protein assemblies to carry out complex tasks. The structural understanding of these efficient nano-machines is often very limited, because conventional techniques like X-ray crystallography or cryo-EM cannot resolve them to sufficient resolution. Firsthand knowledge with cases where the low resolution resulted in limited or even wrong biological conclusions, had led us to the realization that completely unbiased methods are essential. To that end, we developed a combinatorial approach that exhaustively enumerates all the possible arrangements of the biological system and assesses them objectively against the structural data. I will present two such applications on a very suitable system: the eukaryotic chaperonin TRiC/CCT. This large complex is essential to the correct and efficient folding of many proteins in our cells. The overall structure is a spherical particle made of sixteen different subunits, whose exact arrangement was hitherto unknown. We have modeled all the 40,320 possible arrangements and compared them to two sets of structural data: (i) cross-linking and mass-spectrometry and (ii) crystallographic dataset at 3.8.. Both sets have single out the same arrangement, which to our surprise was very different than any previous model suggested for TRiC.