α-crystallin modulates its chaperone activity by varying the exposed surface.

The α-crystallin family of small heat shock proteins possesses chaperone activity in response to stress and is involved in several neurological, muscular, and ophthalmic pathologies. This family includes the vertebrate lens protein α-crystallin, associated with cataract disease. In this study, by combining small-angle X-ray and light scattering techniques, the structure and shape of α-crystallin was revealed in its native state and after a transition caused by heat stress. Below critical temperature (Tc ), α-crystallin appears as an ellipsoid with a central cavity; whereas at high temperatures the cavity almost disappears, and the protein rearranges its structure, increasing the solvent-exposed surface while retaining the ellipsoidal symmetry. Contextually, at Tc , α-crystallin chaperone binding shows an abrupt increase. By modelling the chaperone activity as the formation of a complex composed of α-crystallin and an aggregating substrate, it was demonstrated that the increase of α-crystallin-exposed surface is directly responsible for its gain in chaperone functionality.