The serpins alpha-1-antitrypsin and alpha-1-antichymotrypsin specifically interact with immunophilins.
In a yeast two-hybrid screen FKBP13, a member of the FK506 Binding Protein (FKBP) family, was detected to interact with the serpin alpha-1-antichymotrypsin (ACT). The specificity of the interaction was confirmed in vitro and by the lack of interaction of ACT with FKBP25 and FKBP52. Mutational analysis of ACT revealed that the entire protein is necessary to interact with FKBP13. ACT but also different unrelated small regions of the ACT protein were able to interact with the smaller FKBP12, demonstrating a rather nonspecific interaction with this immunophilin. Naturally occuring mutants of ACT were able to interact as well. Antitrypsin (AT) closely related to ACT did only interfere with FKBP12 a protein that does presumably not reside in the same cellular compartment with AT and ACT. Both serpins interacted with the unrelated immunophilin cyclophilin A. In conclusion the serpin alpha-1-antichymotrypsin physiologically interacts with the ER-immunophilin FKBP13 and the secreted immunophilin cyclophilin A in vivo whereas alpha-1-antitrypsin might only react with cyclophilin A; both serpins may be controlled thereby in their genuine function.
Feldkämper
I
I
Department of Pharmacology, Institute of Medicinal Chemistry, University of Münster, Germany.
Verspohl
E J
EJ
Neye
H
H
D021984:Cyclophilin A / Q000737:chemistry; D017353:Gene Deletion; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D020104:Immunophilins / Q000737:chemistry*; D007166:Immunosuppressive Agents / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D016559:Tacrolimus / Q000494:pharmacology; D022061:Tacrolimus Binding Protein 1A / Q000737:chemistry; D022021:Tacrolimus Binding Proteins / Q000737:chemistry; D000514:alpha 1-Antichymotrypsin / Q000737:chemistry / Q000494:pharmacology*; D000515:alpha 1-Antitrypsin / Q000737:chemistry / Q000494:pharmacology*
D007166:Immunosuppressive Agents; D012333:RNA, Messenger; D000514:alpha 1-Antichymotrypsin; D000515:alpha 1-Antitrypsin; C070133:FKBP-13; D021984:Cyclophilin A; D022061:Tacrolimus Binding Protein 1A; D022021:Tacrolimus Binding Proteins; D020104:Immunophilins; D005978:Glutathione; D016559:Tacrolimus