The alpha-, beta- and gamma-crystallins are the major protein components of the vertebrate eye lens, alpha-crystallin as a molecular chaperone as well as a structural protein, beta- and gamma-crystallins as structural proteins. For the lens to be able to retain life-long transparency in the absence of protein turnover, the crystallins must meet not only the requirement of solubility associated with high cellular concentration but that of longevity as well. For proteins, longevity is commonly assumed to be correlated with long-term retention of native structure, which in turn can be due to inherent thermodynamic stability, efficient capture and refolding of non-native protein by chaperones, or a combination of both. Understanding how the specific interactions that confer intrinsic stability of the protein fold are combined with the stabilizing effect of protein assembly, and how the non-specific interactions and associations of the assemblies enable the generation of highly concentrated solutions, is thus of importance to understand the loss of transparency of the lens with age. Post-translational modification can have a major effect on protein stability but an emerging theme of the few studies of the effect of post-translational modification of the crystallins is one of solubility and assembly. Here we review the structure, assembly, interactions, stability and post-translational modifications of the crystallins, not only in isolation but also as part of a multi-component system. The available data are discussed in the context of the establishment, the maintenance and finally, with age, the loss of transparency of the lens. Understanding the structural basis of protein stability and interactions in the healthy eye lens is the route to solve the enormous medical and economical problem of cataract.

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In its normal state, the eye lens is transparent despite the presence in the cell cytoplasm of high concentrations of proteins, the crystallins, which, a priori, could be expected to scatter an important part of the incident light. Early on, an explanation was sought in the spatial correlations between individual scatterers. Trokel first proposed that the "high concentration of proteins in the lens must be accompanied by a degree of local order approaching a paracrystalline state"; Benedek subsequently suggested that a dense, noncrystalline packing of the proteins would sufficiently reduce the scattered intensity. However, in spite of an improved understanding of the molecular structure of crystallins, their spatial order remained unknown. We present here a small-angle X-ray scattering study of the problem, performed with calf lens cytoplasm both in intact lenses and in cytoplasmic extracts where the crystallin concentration was varied from 3 to 510 mg ml-1. All our experimental data are consistent with short-range spatial order, as in dense liquids or glasses, and this provides a simple explanation for lens transparency. In addition, we detected no conformational change or reorganization of the crystallin proteins throughout the investigated concentration range.

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Lipids as a class encompass a large family of chemical compounds characterized by the presence in the same molecule of a hydrophilic and a hydrophobic part linked together by bonds sufficiently flexible to yield a rather independent behav ior. In the examples mentioned in this review the hydrophobic moiety is formed by one or two hydrocarbon chains of different length and degree of saturation; the hydrophilic groups are more heterogeneous. The following are examples: Soaps: [CH3-(CHz)n_z-Coo-]mxm+; where X is a m-valent cation. Phos pholipids of biological interest: Rl-CO-OCHz I Rz-CO-OCH 0 I I CHz-OPOX I 0-Rl and Rz are hydrocarbon chains; phosphatidic acid: X = H; lecithins: X = CHz-CHz-N+(CH3h ; Iysocompounds: H instead of Rz-CO.One property common to all lipids is the segregation of the hydrophilic and the hydrophobic moieties into distinct regions separated from each other by an interface covered by the polar groups of the lipid molecules. Many of the charac teristic properties of lipids-detergency of soaps, diffusion barrier in biological membranes, and especially the ability to take up a wide variety of structures are direct consequences of this segregation of the polar and apolar parts.Although soaps have a long history in science and technology and synthetic detergents have been studied extensively since the second World War, the first 79 Annu. Rev. Phys. Chem. 1974.25:79-94. Downloaded from www.annualreviews.org by University of Sussex on 10/01/12. For personal use only.Quick links to online content Further ANNUAL REVIEWS 80LUZZATI & TARDIEU significant advances in the structure analysis of lipid-water phases took place as late as the middle 1950s. More recently, the identification and purification of lipid species extracted from biological membranes have become standard labora tory procedures, and developments in lipid chemistry have made an increasing variety of synthetic lipids available. As a consequence, the list of the lipid-water systems studied by X-ray scattering techniques is quite long and continues to grow. The purpose of this article is to review the structure of the phases of lipid water systems, with special emphasis on X-ray scattering studies. Structures will be sorted into three main classes according to the conformation of the hydrocar bon chains-liquid-like, ordered, and mixed. Structures with chains in the liquid-like conformation have been studied quite thoroughly over the last few years and are covered by several review articles (1, 2). In fact, the most inter esting recent developments in this area bear on the molecular movements (3-5) and structure of protein-lipid-water phases (6, 7). Ordered structures, with the chains in a more ordered conformation, are less well known since most of the X-ray ' diffraction studies of these are quite recent. With regard to mixed struc tures involved in the order-disorder conformational transition, structural studies are at a very early stage. Therefore we devote the greater part of this article to ordered and mixed structures. STRUCTURE ANALYS...