Structural and Mechanistic Implications of Metal Binding in the Small Heat-shock Protein αB-crystallin

Abstract

Background: ␣B-crystallin is an ATP-independent chaperone that prevents irreversible protein aggregation. Results: Cu(II) binds to the core domain of ␣B-crystallin, induces increased dynamics at the dimer interface, and thus modulates the anti-aggregation properties of the chaperone. Conclusion:The small heat-shock protein ␣B-crystallin is a metal-regulated chaperone. Significance:The results open new perspectives in the field of protein homeostasis and oxidative stress resistance.

pH-dependent structural modulation is conserved in the human small heat shock protein HSBP1

“…This contrasts with the dramatic increase in chaperone activity reported for the analogous H104 mutation in HSPB5 (Rajagopal et al 2015b) coordinate metal ions (Asthana et al 2014;Mainz et al 2012), the concentration of which may depend on cellular stress conditions. Several charged residues in the HSPB5-ACD, including His104, are implicated in copper and zinc ion binding, and this binding affects dimer stability, oligomeric propensity, and chaperone function (Mainz et al 2012). Although residuespecific interactions with metal ions have not been determined for HSPB1, the residues proposed as ligands in HSPB5 are conserved in HSPB1.…”

Chaperones and chaperone–substrate complexes: Dynamic playgrounds for NMR spectroscopists

“…For the application to chaperone-substrate systems, ssNMR may be a useful method, when the complexes are long-lived. This may be of interest in connection with the sedimentation/FROSTY method, where the chaperone is spun down [114,116,117]. While ssNMR has been applied to study the apo forms of large chaperones [115,118], this method awaits application to chaperone-substrate complexes.…”

“…Furthermore, a relaxation study in both solution and the solid state established that at least two distinct structural environments are adopted by the C-terminal IxI residues of αB-crystallin, one free and one bound, with relative populations varying substantially with temperature [310,311]. To explore the role of copper in the assembly and function of αB-crystallin, a combined solid-state/solution NMR approach was chosen that revealed a copper interaction site with picomolar affinity at the dimer interfaces, as well as structural reorganization of the N-terminus, leading to an increased heterogeneity of the αB-crystallinoligomers [116]. Characterization of the interaction of αB-crystallin with substrates initially showed that the chaperone interacts preferentially with exposed hydrophobic regions as observed in the 1 H spectra of the aromatic region of α-lactalbumin [312].…”

Differential expression and regulation of Cryab in mouse uterus during preimplantation period

“…CRYAA is a lens-specific protein that could protect proteins from aggregation in the eye lens, while CRYAB which was originally discovered in the mammalian eye lens as the B-subunit of a-crystallin is also expressed in a number of non-lenticular tissues, including the heart, skeletal muscles, kidney, lung, brain, placenta, and uterus (Robinson & Overbeek 1996, Gruidl et al 1997, Mineva et al 2008, Mainz et al 2012. In term human placental tissues, CRYAB was visibly observed in the stromal cells of the placental villi (Mineva et al 2008).…”