title: Structure of a Highly Active Cephalopod S-crystallin Mutant: New Molecular Evidence for Evolution from an Active Enzyme into Lens-Refractive Protein.
abstract: Crystallins are found widely in animal lenses and have important functions due to their refractive properties. In the coleoid cephalopods, a lens with a graded refractive index provides good vision and is required for survival. Cephalopod S-crystallin is thought to have evolved from glutathione S-transferase (GST) with various homologs differentially expressed in the lens. However, there is no direct structural information that helps to delineate the mechanisms by which S-crystallin could have evolved. Here we report the structural and biochemical characterization of novel S-crystallin-glutathione complex. The 2.35-Å crystal structure of a S-crystallin mutant from Octopus vulgaris reveals an active-site architecture that is different from that of GST. S-crystallin has a preference for glutathione binding, although almost lost its GST enzymatic activity. We've also identified four historical mutations that are able to produce a "GST-like" S-crystallin that has regained activity. This protein recapitulates the evolution of S-crystallin from GST. Protein stability studies suggest that S-crystallin is stabilized by glutathione binding to prevent its aggregation; this contrasts with GST-σ, which do not possess this protection. We suggest that a tradeoff between enzyme activity and the stability of the lens protein might have been one of the major driving force behind lens evolution.
authors: Department of Life Sciences and Institute of Genome Sciences, National Yang-Ming University, Taipei 112, Taiwan.
authors: Wei-Hung
authors: WH
authors: Tan
authors: Department of Life Sciences and Institute of Genome Sciences, National Yang-Ming University, Taipei 112, Taiwan.
authors: Shu-Chun
authors: SC
authors: Cheng
authors: Department of Life Sciences and Institute of Genome Sciences, National Yang-Ming University, Taipei 112, Taiwan.
authors: Yu-Tung
authors: YT
authors: Liu
authors: Department of Life Sciences and Institute of Genome Sciences, National Yang-Ming University, Taipei 112, Taiwan.
authors: Cheng-Guo
authors: CG
authors: Wu
authors: Department of Life Sciences and Institute of Genome Sciences, National Yang-Ming University, Taipei 112, Taiwan.
authors: Min-Han
authors: MH
authors: Lin
authors: Department of Life Sciences and Institute of Genome Sciences, National Yang-Ming University, Taipei 112, Taiwan.
authors: Chiao-Che
authors: CC
authors: Chen
authors: Department of Life Sciences and Institute of Genome Sciences, National Yang-Ming University, Taipei 112, Taiwan.
authors: Chao-Hsiung
authors: CH
authors: Lin
authors: Department of Life Sciences and Institute of Genome Sciences, National Yang-Ming University, Taipei 112, Taiwan.
authors: Chi-Yuan
authors: CY
authors: Chou
mesh_terms: D000818:Animals; D003459:Crystallins / Q000737:chemistry / Q000235:genetics; D018360:Crystallography, X-Ray; D019143:Evolution, Molecular; D005982:Glutathione Transferase / Q000737:chemistry / Q000235:genetics; D009154:Mutation; D049831:Octopodiformes / Q000737:chemistry / Q000235:genetics; D000072417:Protein Domains
chemical_list: D003459:Crystallins; C117528:S-crystallin protein, Octopus; D005982:Glutathione Transferase