The crowding inherent within cells may affect not only protein movement and folding, but also shape, according to Pernilla Wittung-Stafshede at Rice University in Houston, Texas, and her colleagues.
They focused on the VlsE protein, a proposed virulence factor in Borrelia burgdorferi, the bacterium that causes Lyme disease. VlsE is usually rugby-ball shaped, but the team found that it adopts different equilibrium shapes in vitro in the presence of varying levels of a polymeric 'crowding agent' that mimics cytoplasmic macromolecules. When the native protein is loosened up by a denaturing agent or by heat, two new structures — a 'bean' shape and a roughly spherical conformation — intervene between the rugby ball and the denatured protein as soon as the crowding agent is added.
If crowding can be 'tuned', it might be possible to expose different sites in proteins and alter their behaviour.