Metal-free superoxide dismutase-1 and three different amyotrophic lateral sclerosis variants share a similar partially unfolded beta-barrel at physiological temperature.

ABSTRACT: The structure and unfolding of metal-free (apo) human wild-type SOD1 and three pathogenic variants of SOD1 (A4V, G93R, and H48Q) that cause familial amyotrophic lateral sclerosis have been studied with amide hydrogen/deuterium exchange and mass spectrometry. The results indicate that a significant proportion of each of these proteins exists in solution in a conformation in which some strands of the beta-barrel (i.e. beta2) are well protected from exchange at physiological temperature (37 degrees C), whereas other strands (i.e. beta3 and beta4) appear to be unprotected from hydrogen/deuterium exchange. Moreover, the thermal unfolding of these proteins does not result in the uniform incorporation of deuterium throughout the polypeptide but involves the local unfolding of different residues a

SUBMITTER: Durazo A 

PROVIDER: S-EPMC2797206 | biostudies-literature | 2009 Dec

REPOSITORIES: biostudies-literature