Solid-state NMR and SAXS studies provide a structural basis for the activation of alphaB-crystallin oligomers.
Related Articles Solid-state NMR and SAXS studies provide a structural basis for the activation of alphaB-crystallin oligomers.
Nat Struct Mol Biol. 2010 Aug 29;
Authors: Jehle S, Rajagopal P, Bardiaux B, Markovic S, Kühne R, Stout JR, Higman VA, Klevit RE, van Rossum BJ, Oschkinat H
The small heat shock protein alphaB-crystallin (alphaB) contributes to cellular protection against stress. For decades, high-resolution structural studies on oligomeric alphaB have been confounded by its polydisperse nature. Here, we present a structural basis of oligomer assembly and activation of the chaperone using solid-state NMR and small-angle X-ray scattering (SAXS). The basic building block is a curved dimer, with an angle of approximately 121 degrees between the planes of the beta-sandwich formed by alpha-crystallin domains. The highly conserved IXI motif covers a substrate binding site at pH 7.5. We observe a pH-dependent modulation of the interaction of the IXI motif with beta4 and beta8, consistent with a pH-dependent regulation of the chaperone function. N-terminal region residues Ser59-Trp60-Phe61 are involved in intermolecular interaction with beta3. Intermolecular restraints from NMR and volumetric restraints from SAXS were combined to calculate a model of a 24-subunit alphaB oligomer with tetrahedral symmetry.
PMID: 20802487 [PubMed - as supplied by publisher]
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PubMed