לוח שנה משולב

We think of proteins as ensembles of several mutually-interconverting conformations, and therefore protein 'structure' actually refers to a weighted representation of all conformers contributing to protein behavior. Less intuitive yet very important is the fact that the biological function of proteins depends sometimes upon elusive minor conformers that might be overlooked by a superficial static view. This realization has pushed bio-NMR, a leading solution-based structural method, to the forefront of efforts to identify and, if possible, actually 'see' lowly-populated conformations. The ability of high-resolution NMR to follow and characterize these nearly invisible unsung heroes of protein function will be demonstrated using three case-studies from our research group, (i) intrinsically disordered proteins that challenge the fundamental structure-function dogma, (ii) an under-appreciated pH-dependent oligomerization domain, and (iii) inhibition of a potassium channel by a marine toxin. Together these examples highlight the versatility of solution NMR in illuminating the molecular basis of biological functions involving protein conformational flexibility.