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Structure of the N-terminal domain of human FKBP52.
Acta Crystallogr D Biol Crystallogr. 2003 Jan; 59(Pt 1):16-22.AC

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+Show Affiliations

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.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

12499534

Citation

Li, Pengyun, et al. "Structure of the N-terminal Domain of Human FKBP52." Acta Crystallographica. Section D, Biological Crystallography, vol. 59, no. Pt 1, 2003, pp. 16-22.
Li P, Ding Y, Wu B, et al. Structure of the N-terminal domain of human FKBP52. Acta Crystallogr D Biol Crystallogr. 2003;59(Pt 1):16-22.
Li, P., Ding, Y., Wu, B., Shu, C., Shen, B., & Rao, Z. (2003). Structure of the N-terminal domain of human FKBP52. Acta Crystallographica. Section D, Biological Crystallography, 59(Pt 1), 16-22.
Li P, et al. Structure of the N-terminal Domain of Human FKBP52. Acta Crystallogr D Biol Crystallogr. 2003;59(Pt 1):16-22. PubMed PMID: 12499534.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Structure of the N-terminal domain of human FKBP52. AU - Li,Pengyun, AU - Ding,Yi, AU - Wu,Beili, AU - Shu,Cuiling, AU - Shen,Beifen, AU - Rao,Zihe, Y1 - 2002/12/19/ PY - 2002/06/26/received PY - 2002/09/24/accepted PY - 2002/12/25/pubmed PY - 2003/7/23/medline PY - 2002/12/25/entrez SP - 16 EP - 22 JF - Acta crystallographica. Section D, Biological crystallography JO - Acta Crystallogr D Biol Crystallogr VL - 59 IS - Pt 1 N2 - 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. SN - 0907-4449 UR - https://www.unboundmedicine.com/medline/citation/12499534/Structure_of_the_N_terminal_domain_of_human_FKBP52_ L2 - http://scripts.iucr.org/cgi-bin/paper?S0907444902017523 DB - PRIME DP - Unbound Medicine ER -