Domain metastability: a molecular basis for immunoglobulin deposition?

J Mol Biol. 2010 Jun 4;399(2):207-13. doi: 10.1016/j.jmb.2010.04.011. Epub 2010 Apr 13.

Abstract

We present the crystal structure of an immunoglobulin light-chain-like domain, CTLA-4, as a strand-swapped dimer displaying cis-trans proline isomerisation and native-like hydrogen bonding. We also show that CTLA-4 can form amyloid-like fibres and amorphous deposits explainable by the same strand swapping. Our results suggest a molecular basis for the pathological aggregation of immunoglobulin domains and why amyloid-like fibres are more often composed of homologous rather than heterologous subunits.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Amyloid / chemistry
  • Amyloid / metabolism
  • Antigens, CD / chemistry*
  • Antigens, CD / metabolism
  • CTLA-4 Antigen
  • Crystallography, X-Ray
  • Dimerization
  • Humans
  • Immunoglobulin Light Chains / chemistry*
  • Immunoglobulin Light Chains / metabolism
  • Macromolecular Substances / chemistry
  • Microscopy, Electron
  • Models, Molecular
  • Protein Binding
  • Protein Structure, Quaternary
  • Protein Structure, Tertiary

Substances

  • Amyloid
  • Antigens, CD
  • CTLA-4 Antigen
  • CTLA4 protein, human
  • Immunoglobulin Light Chains
  • Macromolecular Substances