Domain metastability: a molecular basis for immunoglobulin deposition?
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.
Sonnen
Andreas F-P
AF
Division of Structural Biology, The Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, UK. andreas@strubi.ox.ac.uk
Yu
Chao
C
Evans
Edward J
EJ
Stuart
David I
DI
Davis
Simon J
SJ
Gilbert
Robert J C
RJ
D000682:Amyloid / Q000737:chemistry / Q000378:metabolism; D015703:Antigens, CD / Q000737:chemistry* / Q000378:metabolism; D060908:CTLA-4 Antigen; D018360:Crystallography, X-Ray; D019281:Dimerization; D006801:Humans; D007147:Immunoglobulin Light Chains / Q000737:chemistry* / Q000378:metabolism; D046911:Macromolecular Substances / Q000737:chemistry; D008854:Microscopy, Electron; D008958:Models, Molecular; D011485:Protein Binding; D020836:Protein Structure, Quaternary; D017434:Protein Structure, Tertiary
D000682:Amyloid; D015703:Antigens, CD; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D007147:Immunoglobulin Light Chains; D046911:Macromolecular Substances
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