title: Effects of congenital cataract mutation R116H on alphaA-crystallin structure, function and stability.
abstract: alpha-crystallin is a molecular chaperone that maintains the optical properties of the lens and delays the onset scattering caused by aging-related protein aggregation. In this research, we found that the missense mutation R116H resulted in an altered size distribution, impaired packing of the secondary structures and modified quaternary structure with great hydrophobic exposure. The mutant exhibited a substrate-dependent chaperone (aggregation-inhibition) or anti-chaperone (aggregation-promotion) effect. Equilibrium unfolding experiments indicated that the mutation stabilized an aggregation-prone intermediate which was not populated during the unfolding of the wild-type protein. The accumulation of this intermediate greatly promoted the formation of non-native large oligomers or aggregates during unfolding. These results suggested that both the aggregation of the mutant upon stress and co-deposition with the target proteins were likely to be responsible for the onset of cataract.
authors.affiliation: State Key Laboratory of Biomembrane and Membrane Biotechnology, School of Life Sciences, Tsinghua University, Beijing 100084, PR China.
authors.forename: Min
authors.initials: M
authors.lastname: Pang
authors.forename: Jing-Tan
authors.initials: JT
authors.lastname: Su
authors.forename: Shan
authors.initials: S
authors.lastname: Feng
authors.forename: Zhi-Wei
authors.initials: ZW
authors.lastname: Tang
authors.forename: Feng
authors.initials: F
authors.lastname: Gu
authors.forename: Meng
authors.initials: M
authors.lastname: Zhang
authors.forename: Xu
authors.initials: X
authors.lastname: Ma
authors.forename: Yong-Bin
authors.initials: YB
authors.lastname: Yan
mesh_terms: D019943:Amino Acid Substitution; D002386:Cataract / Q000151:congenital* / Q000235:genetics* / Q000378:metabolism; D002942:Circular Dichroism; D003459:Crystallins / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism; D019791:Guanidine; D006801:Humans; D066298:In Vitro Techniques; D008954:Models, Biological; D018832:Molecular Chaperones / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D008970:Molecular Weight; D050505:Mutant Proteins / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism; D020125:Mutation, Missense; D011489:Protein Denaturation; D017510:Protein Folding; D055503:Protein Multimerization; D055550:Protein Stability; D020836:Protein Structure, Quaternary; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D056811:Unfolded Protein Response
chemical_list: C511246:CRYAA protein, human; D003459:Crystallins; D018832:Molecular Chaperones; D050505:Mutant Proteins; D011994:Recombinant Proteins; D019791:Guanidine