title: The thermal structural transition of alpha-crystallin modulates subunit interactions and increases protein solubility.
abstract: BACKGROUND
  Alpha crystallin is an oligomer composed of two types of subunits, alpha-A and alpha-B crystallin, and is the major constituent of human lens. The temperature induced condensation of alpha-crystallin, the main cause for eye lens opacification (cataract), is a two step-process, a nucleation followed by an aggregation phase, and a protective effect towards the aggregation is exhibited over the alpha crystallin phase transition temperature (Tc = 318.16 K).
  
  
  RESULTS
  To investigate if a modulation of the subunit interactions over Tc could trigger the protective mechanism towards the aggregation, we followed, by using simultaneously static and dynamic light scattering, the temperature induced condensation of alpha-crystallin. By developing a mathematical model able to uncouple the nucleation and aggregation processes, we find a previously unobserved transition in the nucleation rate constant. Its temperature dependence allows to determine fundamental structural parameters, the chemical potential (Δμ) and the interfacial tension (γ) of the aggregating phase, that characterize subunit interactions.
  The decrease of both Δμ and γ at Tc, and a relative increase in solubility, reveal a significative decrease in the strenght of alpha-crystallin subunits interactions, which protects from supramolecolar condensation in hypertermic conditions. On the whole, we suggest a general approach able to understand the structural and kinetic mechanisms involved in aggregation-related diseases and in drugs development and testing.
authors.affiliation: Istituto di Fisica, Università Cattolica del Sacro Cuore, Roma, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Maulucci
authors.forename: Marco
authors.initials: M
authors.lastname: De Spirito
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Arcovito
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Papi
mesh_terms: D002386:Cataract; D006801:Humans; D007700:Kinetics; D044367:Phase Transition; D055503:Protein Multimerization; D021122:Protein Subunits; D012542:Scattering, Radiation; D012995:Solubility; D013500:Surface Tension; D013696:Temperature; D013816:Thermodynamics; D038201:alpha-Crystallins / Q000737:chemistry* / Q000378:metabolism
chemical_list: D021122:Protein Subunits; D038201:alpha-Crystallins