title: Structure of the N-terminal domain of human FKBP52.
abstract: FKBP52 is a member of the FK506-binding protein family (FKBPs). The N-terminal domain of FKBP52 (FKBP52-N; residues 1-140) is responsible for peptidyl-prolyl isomerase activity and binding of FK506. Here, the crystal structure of FKBP52-N has been determined by molecular replacement to 2.4 A. FKBP52-N is defined by a six-stranded antiparallel beta-sheet wrapping with a right-handed twist around a short alpha-helix, an architecture similar to that of FKBP12. FKBP52-N is able to bind FK506 in a similar way to FKBP12. The variability in two loop regions (residues 70-76 and 108-127) is the principal reason for the specificity differences between FKBP52-N and FKBP12. The Pro120 change corresponding to Gly89 in FKBP12 limits the conformational adaptation between the loop (residues 108-127) and FK506 and decreases the FK506 affinity, while the Lys121 substitution corresponding to Ile90 of FKBP12 destroys a key interaction between FKBP52-N and calcineurin. It can be inferred from the locations of strictly conserved amino acids in the polypeptide chain that the maintenance of the overall conformation of the PPIase domains of FKBPs is essential for the PPIase activity. The N-terminal region and beta-sheets of FKBP52-N forms a hydrophobic patch which may be responsible for the binding of target proteins such as dynein or PAHX.
authors.affiliation: MOE Laboratory of Protein Science and Laboratory of Structural Biology, Department of Biological Science and Biotechnology, Tsinghua University, Beijing 100084, People's Republic of China.
authors.forename: Pengyun
authors.initials: P
authors.lastname: Li
authors.forename: Yi
authors.initials: Y
authors.lastname: Ding
authors.forename: Beili
authors.initials: B
authors.lastname: Wu
authors.forename: Cuiling
authors.initials: C
authors.lastname: Shu
authors.forename: Beifen
authors.initials: B
authors.lastname: Shen
authors.forename: Zihe
authors.initials: Z
authors.lastname: Rao
mesh_terms: D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D001665:Binding Sites; D017124:Conserved Sequence; D018360:Crystallography, X-Ray; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D019696:Peptidylprolyl Isomerase / Q000378:metabolism; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid; D013379:Substrate Specificity; D016559:Tacrolimus / Q000378:metabolism; D022061:Tacrolimus Binding Protein 1A / Q000737:chemistry / Q000378:metabolism; D022021:Tacrolimus Binding Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism
chemical_list: D022061:Tacrolimus Binding Protein 1A; D022021:Tacrolimus Binding Proteins; C403485:tacrolimus binding protein 4; D019696:Peptidylprolyl Isomerase; D016559:Tacrolimus