The structure of the cataract-causing P23T mutant of human gammaD-crystallin exhibits distinctive local conformational and dynamic changes.

ABSTRACT: Crystallins are major proteins of the eye lens and essential for lens transparency. Mutations and aging of crystallins cause cataracts, the predominant cause of blindness in the world. In human gammaD-crystallin, the P23T mutant is associated with congenital cataracts. Until now, no atomic structural information has been available for this variant. Biophysical analyses of this mutant protein have revealed dramatically reduced solubility compared to that of the wild-type protein due to self-association into higher-molecular weight clusters and aggregates that retain a nativelike conformation within the monomers [Pande, A., et al. (2005) Biochemistry 44, 2491-2500]. To elucidate the structure and local conformation around the mutation site, we have determined the solution structure and chara

SUBMITTER: Jung J 

PROVIDER: S-EPMC2722838 | biostudies-literature | 2009 Mar

REPOSITORIES: biostudies-literature