Edinburgh Research Explorer

The structure and oxidation of the eye lens chaperone αA-crystallin

Research output: Contribution to journalArticle

  • Christoph J.O. Kaiser
  • Carsten Peters
  • Philipp W.N. Schmid
  • Maria Stavropoulou
  • Juan Zou
  • Vinay Dahiya
  • Evgeny V. Mymrikov
  • Beate Rockel
  • Sam Asami
  • Martin Haslbeck
  • Juri Rappsilber
  • Bernd Reif
  • Martin Zacharias
  • Johannes Buchner
  • Sevil Weinkauf

Related Edinburgh Organisations

Original languageEnglish
Pages (from-to)1141-1150
Number of pages10
JournalNature Structural and Molecular Biology
Volume26
Issue number12
DOIs
Publication statusPublished - 2 Dec 2019

Abstract

The small heat shock protein αA-crystallin is a molecular chaperone important for the optical properties of the vertebrate eye lens. It forms heterogeneous oligomeric ensembles. We determined the structures of human αA-crystallin oligomers by combining cryo-electron microscopy, cross-linking/mass spectrometry, NMR spectroscopy and molecular modeling. The different oligomers can be interconverted by the addition or subtraction of tetramers, leading to mainly 12-, 16- and 20-meric assemblies in which interactions between N-terminal regions are important. Cross-dimer domain-swapping of the C-terminal region is a determinant of αA-crystallin heterogeneity. Human αA-crystallin contains two cysteines, which can form an intramolecular disulfide in vivo. Oxidation in vitro requires conformational changes and oligomer dissociation. The oxidized oligomers, which are larger than reduced αA-crystallin and destabilized against unfolding, are active chaperones and can transfer the disulfide to destabilized substrate proteins. The insight into the structure and function of αA-crystallin provides a basis for understanding its role in the eye lens.

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