Some properties of G84R and L99M mutants of HspB1 associated with peripheral distal neuropathies were investigated. Homooligomers formed by these mutants are larger than those of the wild type HspB1. Large oligomers of G84R and L99M mutants have compromised stability and tend to dissociate at low protein concentration. G84R and L99M mutations promote phosphorylation-dependent dissociation of HspB1 oligomers without affecting kinetics of HspB1 phosphorylation by MAPKAP2 kinase. Both mutants weakly interact with HspB6 forming small heterooligomers and being unable to form large heterooligomers characteristic for the wild type HspB1. G84R and L99M mutants possess lower chaperone-like activity than the wild type HspB1 with several model substrates. We suggest that G84R mutation affects mobility and accessibility of the N-terminal domain thus modifying interdimer contacts in HspB1 oligomers. The L99M mutation is located within the hydrophobic core of the á-crystallin domain close to the key R140 residue, and could affect the dimer stability.
Amino Acid Sequence Dimerization