The chaperone αB-crystallin uses different interfaces to capture an amorphous and an amyloid client

Andi Mainz, Jirka Peschek, Maria Stavropoulou, Katrin C Back, Benjamin Bardiaux, Sam Asami, Elke Prade, Carsten Peters, Sevil Weinkauf, Johannes Buchner, Bernd Reif
2015 Nature Structural & Molecular Biology  
Small heat-shock proteins, among them αB-crystallin (αB), play an important role in protein homeostasis, as their ATP-independent chaperone activity inhibits uncontrolled protein aggregation. Mechanistic details of human αB, in particular in its client-bound state, were elusive so far due to the high molecular weight and the heterogeneity of these complexes. Here we provide structural insights into this highly dynamic assembly and show -using state-of-the-art NMR spectroscopy -that the αB
more » ... -that the αB complex is assembled from asymmetric building blocks. Interaction studies demonstrate that the fibril-forming Alzheimer's disease Aβ1-40 peptide preferentially binds to a hydrophobic edge of the central β-sandwich of αB. By contrast, the amorphously aggregating client lysozyme is captured by the partially-disordered N-terminal domain of αB. We suggest that αB utilizes its inherent structural plasticity to expose distinct binding interfaces to interact with a wide range of structurally variable clients.
doi:10.1038/nsmb.3108 pmid:26458046 fatcat:vfnsxyerkngf7deg275gdalieq