title: Mouse FKBP23 mediates conformer-specific functions of BiP by catalyzing Pro117 cis/trans isomerization.
abstract: FK506-binding proteins (FKBPs) are cellular receptors for the immunosuppressant FK506 and rapamycin. They belong to the ubiquitous peptidyl-prolyl cis/trans isomerases (PPIases) family, which can catalyze the cis/trans isomerization of peptidyl-prolyl bond in peptides and proteins. In previous work, we revealed that mouse FKBP23 binds immunoglobulin binding protein (BiP), the major heat shock protein (Hsp) 70 chaperone in the ER, and the binding is interrelated with [Ca(2+)]. Furthermore, the binding can suppress the ATPase activity of BiP through the PPIase activity of FKBP23. In this work, FKBP23 is demonstrated to mediate functions of BiP by catalyzing the Pro(117)cis/trans conformational interconversion in the ATPase domain of BiP. This result may provide new understanding to the novel role of PPIase as a molecular switch.
authors.affiliation: Biochemical Section of Key Laboratory of Functional Polymer Materials, The Ministry of Education of China, Chemical School of Nankai University, Tianjin, PR China.
authors.forename: Miao
authors.initials: M
authors.lastname: Feng
authors.forename: Chao
authors.initials: C
authors.lastname: Gu
authors.forename: Shikui
authors.initials: S
authors.lastname: Ma
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.forename: Huijuan
authors.initials: H
authors.lastname: Liu
authors.forename: Ruifang
authors.initials: R
authors.lastname: Han
authors.forename: Junfei
authors.initials: J
authors.lastname: Gao
authors.forename: Yi
authors.initials: Y
authors.lastname: Long
authors.forename: Huaifeng
authors.initials: H
authors.lastname: Mi
mesh_terms: D000818:Animals; D002135:Calcium-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D002384:Catalysis; D000091342:Endoplasmic Reticulum Chaperone BiP; D006360:Heat-Shock Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D007536:Isomerism; D007930:Leucine / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D019696:Peptidylprolyl Isomerase / Q000737:chemistry / Q000378:metabolism*; D011392:Proline / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D011487:Protein Conformation; D013379:Substrate Specificity; D022021:Tacrolimus Binding Proteins / Q000737:chemistry / Q000378:metabolism*
chemical_list: D002135:Calcium-Binding Proteins; D000091342:Endoplasmic Reticulum Chaperone BiP; C116295:Fkbp7 protein, mouse; D006360:Heat-Shock Proteins; D011392:Proline; D022021:Tacrolimus Binding Proteins; D019696:Peptidylprolyl Isomerase; D007930:Leucine