Domain metastability: a molecular basis for immunoglobulin deposition?

Journal article

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.

Authors: Sonnen, A; Yu, C; Evans, E; Stuart, D; Davis, S

• Publication status: Published
• Journal: Journal of molecular biology
• Volume: 399
• Issue: 2
• Pages: 207-213
• Publication date: 2010-06-01
• DOI: 10.1016/j.jmb.2010.04.011
• EISSN: 1089-8638
• ISSN: 0022-2836
• Language: English
• Keywords: Antigens, CD; CTLA-4 Antigen; Models, Molecular; Amyloid; Humans; Dimerization; Crystallography, X-Ray; Protein Binding; Microscopy, Electron; Protein Structure, Quaternary; Macromolecular Substances; Immunoglobulin Light Chains; Protein Structure, Tertiary