Identification of the key structural motifs involved in HspB8/HspB6–Bag3 interaction

• DOI: 10.1042/bj20090907
• Publication Date: 2009-10-22T10:18:41Z
• Authors: Margit Fuchs; Dominic J. Poirier; Samuel J. Seguin; Herman Lambert; Serena Carra; Steve J. Charette; Jacques Landry
• Keywords: BAG3; WW domain; Co-chaperone; Chaperone (clinical); HEK 293 cells

The molecular chaperone HspB8 [Hsp (heat-shock protein) B8] is member of the B-group Hsps. These proteins bind to unfolded or misfolded and protect them from aggregation. has been reported form a stable complex with cohort protein Bag3 (Bcl-2-associated athanogene 3). In present study we identify binding regions in crucial for their interaction. We evidence that binds through hydrophobic groove formed by its strands beta4 beta8, region previously known be responsible formation stability higher-order oligomers many sHsps (small Hsps). Moreover, demonstrate two conserved IPV (Ile-Pro-Val) motifs mediate deletion these suppresses activity towards mutant Htt43Q (huntingtin exon 1 fragment 43 CAG repeats). addition, show can HspB6. interaction between HspB6 requires same are involved HspB8-Bag3 association HspB6-Bag3 promotes clearance aggregated Htt43Q. Our findings suggest co-chaperone might prevent accumulation denatured regulating sHsp targeting substrate degradation. Interestingly, mutation one recently associated development severe dominant childhood muscular dystrophy, suggesting possible important physiological role HspB-Bag3 complexes this disease.