alpha-Crystallin quaternary structure and interactive properties control eye lens transparency.

The eye lens is the foremost biological system where function is directly under control of the physico-chemical properties of the cytoplasmic macromolecular solution. Indeed, lens transparency and opacity, lens refractive index gradient and viscosity, are the result of the structural and interactive properties of the crystallins, of their stability, of the fine tuning of their interaction potentials and associations at different levels of organization. Among the different crystallin classes, alpha-crystallins have represented a major challenge for a long time. The alpha-crystallin secondary, tertiary and quaternary structures are still unknown. On the functional side, however, it is established that alpha-crystallin quaternary structure and repulsive interactions determine lens transparency, whereas the alpha-crystallin chaperone effect most probably plays a role in the aging process. In the present paper, we recall the physico-chemical properties and the quaternary structure features of alpha-crystallins that were demonstrated to control light scattering and transparency. The interest of a crystallin mixture for lens function is discussed. Then, a formal approach is proposed to design models for the alpha-crystallin quaternary structure, including the question of whether alpha-crystallins assemble with symmetry. An hypothesis relevant to the fold of the alpha-crystallin C-terminal domain is presented in another paper in this issue.