title: Functional role of the flexible N-terminal extension of FKBP38 in catalysis.
abstract: FKBP38 regulates apoptosis through unique interactions with multiple regulators including Bcl-2. Interestingly, the peptidylprolyl isomerase activity of FKBP38 is only detectable when it binds to calcium-saturated calmodulin (CaM/Ca(2+)). This, in turn, permits the formation of a complex with Bcl-2. FKBP38 thereby provides an important link between isomerase activity and apoptotic pathways. Here, we show that the N-terminal extension (residues 1-32) preceding the catalytic domain of FKBP38 has an autoinhibitory activity. The core isomerase activity of FKBP38 is inhibited by transient interactions involving the flexible N-terminal extension that precedes the catalytic domain. Notably, CaM/Ca(2+) binds to this N-terminal extension and thereby releases the autoinhibitory contacts between the N-terminal extension and the catalytic domain, thus potentiating the isomerase activity of FKBP38. Our data demonstrate how CaM/Ca(2+) modulates the catalytic activity of FKBP38.
authors.affiliation: 1] School of Biological Science, Nanyang Technological University, 60 Nanyang Drive, Singapore 637551, Singapore [2] [3].
authors.forename: Congbao
authors.initials: C
authors.lastname: Kang
authors.forename: Hong
authors.initials: H
authors.lastname: Ye
authors.forename: Joel
authors.initials: J
authors.lastname: Chia
authors.forename: Bo-Hwa
authors.initials: BH
authors.lastname: Choi
authors.forename: Sirano
authors.initials: S
authors.lastname: Dhe-Paganon
authors.forename: Bernd
authors.initials: B
authors.lastname: Simon
authors.forename: Ulrike
authors.initials: U
authors.lastname: Schütz
authors.forename: Michael
authors.initials: M
authors.lastname: Sattler
authors.forename: Ho Sup
authors.initials: HS
authors.lastname: Yoon
mesh_terms: D000595:Amino Acid Sequence; D002118:Calcium / Q000378:metabolism; D002147:Calmodulin / Q000378:metabolism; D002384:Catalysis; D004789:Enzyme Activation; D006801:Humans; D007700:Kinetics; D008954:Models, Biological; D008958:Models, Molecular; D008969:Molecular Sequence Data; D008970:Molecular Weight; D046912:Multiprotein Complexes / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D011487:Protein Conformation; D054730:Protein Interaction Domains and Motifs; D016415:Sequence Alignment; D012996:Solutions; D022021:Tacrolimus Binding Proteins / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D002147:Calmodulin; C471205:FKBP8 protein, human; D046912:Multiprotein Complexes; D012996:Solutions; D022021:Tacrolimus Binding Proteins; D002118:Calcium