Selective destabilization of the metal binding region caused by the FALS associated mutation G93A in CuZnSOD

Museth, Anna KatrineLinköpings universitet,Molekylär Bioteknik,Tekniska högskolan (author)

We have, by use of 1H-15N-HSQC NMR spectroscopy, analyzed hydrogen exchange at the amide groups of wtCuZnSOD and the FALS-associated G93A SOD-variant in their fully metallated states. From measurements at near physiological conditions we could analyze the exchange at 64% of all backbone amide groups, which have allowed a detailed characterization of the local dynamics at these positions in both the wt and G93A proteins. The results show that the G93A mutation had no effect on the dynamics at a majority of the investigated positions. However the mutation results in local destabilization at the site of mutation and to stabilization at positions that were apparently scattered over the entire protein surface. Most remarkably, the mutation selectively destabilized the remote metal binding region. The results indicate that the metal binding region may be involved in intermolecular protein-protein interactions, which may constitute the early stages in formation of aggregates.

Brorsson, Anna-ChristinLinköpings universitet,Molekylär Bioteknik,Tekniska högskolan(Swepub:liu)annbr05 (author)
Lundqvist, MartinLinköpings universitet,Molekylär Bioteknik,Tekniska högskolan(Swepub:liu)marlu50 (author)
Tibell, Lena A. E.Linköpings universitet,Cellbiologi,Hälsouniversitetet(Swepub:liu)lenti27 (author)
Jonsson, Bengt-HaraldLinköpings universitet,Molekylär Bioteknik,Tekniska högskolan(Swepub:liu)benjo56 (author)
Linköpings universitetMolekylär Bioteknik (creator_code:org_t)

By the author/editor: Museth, Anna Kat ...; Brorsson, Anna-C ...; Lundqvist, Marti ...; Tibell, Lena A. ...; Jonsson, Bengt-H ...

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