Solid-state NMR and SAXS studies provide a structural basis for the activation of alpha B-crystallin oligomers

Stefan Jehle, Ponni Rajagopal, Benjamin Bardiaux, Stefan Markovic, Ronald Kuehne, Joseph R. Stout, Victoria A. Higman, Rachel E. Klevit*, Barth-Jan van Rossum, Hartmut Oschkinat

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review

202 Citations (Scopus)

Abstract

The small heat shock protein alpha B-crystallin (alpha B) contributes to cellular protection against stress. For decades, high-resolution structural studies on oligomeric alpha B 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 similar to 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 beta 4 and beta 8, consistent with a pH-dependent regulation of the chaperone function. N-terminal region residues Ser59-Trp60-Phe61 are involved in intermolecular interaction with beta 3. Intermolecular restraints from NMR and volumetric restraints from SAXS were combined to calculate a model of a 24-subunit alpha B oligomer with tetrahedral symmetry.

Original languageEnglish
Pages (from-to)1037-U1
Number of pages7
JournalNature Structural and Molecular Biology
Volume17
Issue number9
DOIs
Publication statusPublished - Sep 2010

Keywords

  • SOLUTION SCATTERING
  • SPECTROSCOPY
  • ASSEMBLIES
  • AMYLOID FIBRILS
  • CRYSTALLOGRAPHY
  • HEAT-SHOCK-PROTEIN
  • DOMAIN
  • UCSF CHIMERA
  • CHAPERONE
  • X-RAY SOLUTION

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