|2klr, 10 NMR models ()|
|Gene:||CRYAB, CRYA2 (Homo sapiens)|
Solid-state NMR structure of the alpha-crystallin domain in alphaB-crystallin oligomers
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.
Solid-state NMR and SAXS studies provide a structural basis for the activation of alphaB-crystallin oligomers., Jehle S, Rajagopal P, Bardiaux B, Markovic S, Kuhne R, Stout JR, Higman VA, Klevit RE, van Rossum BJ, Oschkinat H, Nat Struct Mol Biol. 2010 Sep;17(9):1037-42. Epub 2010 Aug 29. PMID:20802487
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
About this Structure
- Jehle S, Rajagopal P, Bardiaux B, Markovic S, Kuhne R, Stout JR, Higman VA, Klevit RE, van Rossum BJ, Oschkinat H. Solid-state NMR and SAXS studies provide a structural basis for the activation of alphaB-crystallin oligomers. Nat Struct Mol Biol. 2010 Sep;17(9):1037-42. Epub 2010 Aug 29. PMID:20802487 doi:10.1038/nsmb.1891
- Jehle S, van Rossum B, Stout JR, Noguchi SM, Falber K, Rehbein K, Oschkinat H, Klevit RE, Rajagopal P. alphaB-crystallin: a hybrid solid-state/solution-state NMR investigation reveals structural aspects of the heterogeneous oligomer. J Mol Biol. 2009 Feb 6;385(5):1481-97. Epub 2008 Nov 14. PMID:19041879 doi:10.1016/j.jmb.2008.10.097