The FK506 binding protein 13 kDa (FKBP13) interacts with the C-chain of complement C1q.
BACKGROUND
The pharmacological action of specific immunosuppressants is mediated by immunophilins. While cyclosporin A binds to cyclophilins, FK506/tacrolimus, rapamycin, and others bind to FK506 binding proteins (FKBPs). Different physiological actions of immunophilins were described but their genuine function, however, remains elusive and is still under investigation. A yeast two-hybrid screen was performed using the FK506 binding protein 13 kDa (FKBP13) as a bait and a fetal liver expression library as a prey.


RESULTS
The C-chain of complement C1q (C1q-C) was detected to interact with FKBP13 in the yeast two-hybrid system and in a protein complementation assay. Neither FKBP12, FKBP25, FKBP52 nor the unrelated immunophilin CypA did react with C1q-C in the yeast system stressing the specificity of the interaction. Binding of C1q-C to FKBP13 could not be prevented in the presence of FK506, demonstrating that possibly other regions than the binding pocket of the drug are responsible for the interaction of the two proteins.


CONCLUSIONS
It is concluded that exclusively FKBP13 but no other FKBPs tested so far interact with the C-chain of complement C1q in the two different assays and further work will be initiated to investigate the physiological relevance of the interaction.
Neye
Holger
H
KV Niedersachsen, Berliner Allee 22, D-30175 Hannover, Germany.
Verspohl
Eugen J
EJ
Institute of Medicinal Chemistry, Dept. of Pharmacology, Hittorfstr. 58-62, D-48149 Münster, Germany.
D000818:Animals; D045744:Cell Line, Tumor; D015922:Complement C1q / Q000378:metabolism*; D021984:Cyclophilin A / Q000276:immunology; D015723:Gene Library; D006801:Humans; D010446:Peptide Fragments / Q000378:metabolism; D011485:Protein Binding / Q000187:drug effects; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000276:immunology; D012441:Saccharomyces cerevisiae; D016559:Tacrolimus / Q000494:pharmacology; D022021:Tacrolimus Binding Proteins / Q000276:immunology*
D010446:Peptide Fragments; D011993:Recombinant Fusion Proteins; C070133:FKBP-13; D015922:Complement C1q; D021984:Cyclophilin A; D022021:Tacrolimus Binding Proteins; D016559:Tacrolimus