3D structure of human FK506-binding protein 52: implications for the assembly of the glucocorticoid receptor/Hsp90/immunophilin heterocomplex.
FK506-binding protein 52 (FKBP52), which binds FK506 and possesses peptidylprolyl isomerase activity, is an important immunophilin involved in the heterocomplex of steroid receptors with heat-shock protein 90. Here we report the crystal structures of two overlapped fragments [N(1-260) and C(145-459)] of FKBP52 and the complex with a C-terminal pentapeptide from heat-shock protein 90. Based on the structures of these two overlapped fragments, the complete putative structure of FKBP52 can be defined. The structure of FKBP52 is composed of two consecutive FKBP domains, a tetratricopeptide repeat domain and a short helical domain beyond the final tetratricopeptide repeat motif. Key structural differences between FKBP52 and FKBP51, including the relative orientations of the four domains and some important residue substitutions, could account for the differential functions of FKBPs.
Wu
Beili
B
Laboratory of Structural Biology, Tsinghua University, Beijing 100084, China.
Li
Pengyun
P
Liu
Yiwei
Y
Lou
Zhiyong
Z
Ding
Yi
Y
Shu
Cuiling
C
Ye
Sheng
S
Bartlam
Mark
M
Shen
Beifen
B
Rao
Zihe
Z
D000595:Amino Acid Sequence; D001665:Binding Sites; D018360:Crystallography, X-Ray; D018841:HSP90 Heat-Shock Proteins / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D006860:Hydrogen Bonding; D046911:Macromolecular Substances; D008958:Models, Molecular; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary; D011965:Receptors, Glucocorticoid / Q000737:chemistry* / Q000378:metabolism; D016415:Sequence Alignment; D022021:Tacrolimus Binding Proteins / Q000737:chemistry* / Q000378:metabolism; D000099159:Tacrolimus Binding Protein 5
D018841:HSP90 Heat-Shock Proteins; D046911:Macromolecular Substances; D011965:Receptors, Glucocorticoid; D022021:Tacrolimus Binding Proteins; D000099159:Tacrolimus Binding Protein 5; C403485:tacrolimus binding protein 4