Structural and functional specificity of small heat shock protein HspB1 and HspB4, two cellular partners of HspB5: Role of the in vitro hetero-complex formation in chaperone activity

• Published in: Biochimie 2012-04, Vol.94 (4), p.975-984
• Main Authors: Skouri-Panet, Fériel, Michiel, Magalie, Férard, Céline, Duprat, Elodie, Finet, Stéphanie
• Format: Article
• Language: English
• Subjects: alpha-Crystallin B Chain - chemistry; alpha-Crystallin B Chain - isolation & purification; Animals; Cattle; Chaperone activity; Chromatography, Gel; Crystallins - chemistry; Crystallins - isolation & purification; HSP27 Heat-Shock Proteins - chemistry; HSP27 Heat-Shock Proteins - isolation & purification; HspB1–HspB4–HspB5 oligomers; Humans; Light; Mammal small heat shock proteins; Protein Multimerization; Protein Stability; Protein Structure, Quaternary; Protein Subunits - chemistry; Protein Subunits - isolation & purification; Recombinant Proteins - chemistry; Recombinant Proteins - isolation & purification; Scattering, Radiation; Scattering, Small Angle; Sequence analysis; Sequence Analysis, Protein; Sequence Homology, Amino Acid; X-ray and light scattering; X-Ray Diffraction
• ISSN: 0300-9084; 1638-6183
• DOI: 10.1016/j.biochi.2011.12.018

The ubiquitous small heat shock proteins are essential elements in cellular protection, through a molecular chaperone activity. Among them, human small heat shock protein HspB1, HspB4 and HspB5 are involved in oncogenesis, anti-apoptotic activity and lens transparency. Therefore, these proteins are potential therapeutic targets in many diseases. Their general chaperone activity is related to their dynamic and multiple oligomeric structures, which are still poorly understood. The tissue selective distribution of HspB1 and HspB4, two cellular partners of HspB5, suggests that these two proteins might have evolved to play distinct physiological functions. Moreover, hetero-complex formation seems to be favoured in vivo, yet the functional specificity of the HspB1–HspB5 and HspB4–HspB5 hetero-complexes compared to the homo-oligomers remains unclear in the stress response pathway. A powerful approach combining biochemistry, biophysics and bioinformatics, allowed us to compare the different assemblies, with a special emphasis on the structural data, subunit exchange properties, activity and sequence evolution. We showed that they all exhibit different properties, from structural organization in physiological versus stress conditions, to chaperone-like activity, whatever the level of sequence conservation. Subunit exchange kinetics leading to HspB1–HspB5 or HspB4–HspB5 hetero-complex formation is also different between these two complexes: HspB5 exchanges more rapidly subunits with HspB1 than with HspB4. The relative sequence conservation in the sHSP superfamily does hide important structural heterogeneity and flexibility, which confer an enlarged range of different surface necessary to efficiently form complexes with various stress-induced cellular targets. Our data suggest that the formation of hetero-complexes could be an original evolutionary strategy to gain new cellular functions. [Display omitted] ► HspB1 subunit exchange is faster than HspB4 and HspB5. ► Mammal HspB1 share more sequence variability, in particular for the extensions. ► Lens specific HspB4 exhibits lowest oligomerization and polydispersity at physiological conditions. ► New hetero-complexes are formed through the sHSP subunit exchange process. ► Hetero-complexes are functional and could have gained in efficiency.