BAG3 directly interacts with mutated alphaB-crystallin to suppress its aggregation and toxicity.
A homozygous disruption or genetic mutation of the bag3 gene causes progressive myofibrillar myopathy in mouse and human skeletal and cardiac muscle disorder while mutations in the small heat shock protein αB-crystallin gene (CRYAB) are reported to be responsible for myofibrillar myopathy. Here, we demonstrate that BAG3 directly binds to ... wild-type αB-crystallin and the αB-crystallin mutant R120G, via the intermediate domain of BAG3. Peptides that inhibit this interaction in an in vitro binding assay indicate that two conserved Ile-Pro-Val regions of BAG3 are involved in the interaction with αB-crystallin, which is similar to results showing BAG3 binding to HspB8 and HspB6. BAG3 overexpression increased αB-crystallin R120G solubility and inhibited its intracellular aggregation in HEK293 cells. BAG3 suppressed cell death induced by αB-crystallin R120G overexpression in differentiating C2C12 mouse myoblast cells. Our findings indicate a novel function for BAG3 in inhibiting protein aggregation caused by the genetic mutation of CRYAB responsible for human myofibrillar myopathy.
Mesh Terms:
Adaptor Proteins, Signal Transducing, Amino Acid Sequence, Amino Acid Substitution, Animals, Cell Line, Humans, Mice, Molecular Sequence Data, Mutant Proteins, Mutation, Protein Binding, Protein Folding, Protein Structure, Quaternary, Protein Structure, Tertiary, Rats, Solubility, alpha-Crystallin B Chain
Adaptor Proteins, Signal Transducing, Amino Acid Sequence, Amino Acid Substitution, Animals, Cell Line, Humans, Mice, Molecular Sequence Data, Mutant Proteins, Mutation, Protein Binding, Protein Folding, Protein Structure, Quaternary, Protein Structure, Tertiary, Rats, Solubility, alpha-Crystallin B Chain
PLoS ONE
Date: Mar. 23, 2011
PubMed ID: 21423662
View in: Pubmed Google Scholar
Download Curated Data For This Publication
146827
Switch View:
- Interactions 6