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Structure of the large FK506-binding protein FKBP51, an Hsp90-binding protein and a component of steroid receptor complexes.
Proc Natl Acad Sci U S A. 2003 Feb 04; 100(3):868-73.PN

Abstract

The ability to bind immunosuppressive drugs such as cyclosporin and FK506 defines the immunophilin family of proteins, and the FK506-binding proteins form the FKBP subfamily of immunophilins. Some FKBPs, notably FKBP12 (the 12-kDa FK506-binding protein), have defined roles in regulating ion channels or cell signaling, and well established structures. Other FKBPs, especially the larger ones, participate in important biological processes, but their exact roles and the structural bases for these roles are poorly defined. FKBP51 (the 51-kDa FKBP) associates with heat shock protein 90 (Hsp90) and appears in functionally mature steroid receptor complexes. In New World monkeys, FKBP51 has been implicated in cortisol resistance. We report here the x-ray structures of human FKBP51, to 2.7 A, and squirrel monkey FKBP51, to 2.8 A, by using multiwavelength anomalous dispersion phasing. FKBP51 is composed of three domains: two consecutive FKBP domains and a three-unit repeat of the TPR (tetratricopeptide repeat) domain. This structure of a multi-FKBP domain protein clarifies the arrangement of these domains and their possible interactions with other proteins. The two FKBP domains differ by an insertion in the second that affects the formation of the progesterone receptor complex.

Authors+Show Affiliations

Department of Chemistry and Chemical Biology, Cornell University, Ithaca, NY 14853-1301, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, Non-P.H.S.
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

12538866

Citation

Sinars, Cindy R., et al. "Structure of the Large FK506-binding Protein FKBP51, an Hsp90-binding Protein and a Component of Steroid Receptor Complexes." Proceedings of the National Academy of Sciences of the United States of America, vol. 100, no. 3, 2003, pp. 868-73.
Sinars CR, Cheung-Flynn J, Rimerman RA, et al. Structure of the large FK506-binding protein FKBP51, an Hsp90-binding protein and a component of steroid receptor complexes. Proc Natl Acad Sci U S A. 2003;100(3):868-73.
Sinars, C. R., Cheung-Flynn, J., Rimerman, R. A., Scammell, J. G., Smith, D. F., & Clardy, J. (2003). Structure of the large FK506-binding protein FKBP51, an Hsp90-binding protein and a component of steroid receptor complexes. Proceedings of the National Academy of Sciences of the United States of America, 100(3), 868-73.
Sinars CR, et al. Structure of the Large FK506-binding Protein FKBP51, an Hsp90-binding Protein and a Component of Steroid Receptor Complexes. Proc Natl Acad Sci U S A. 2003 Feb 4;100(3):868-73. PubMed PMID: 12538866.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Structure of the large FK506-binding protein FKBP51, an Hsp90-binding protein and a component of steroid receptor complexes. AU - Sinars,Cindy R, AU - Cheung-Flynn,Joyce, AU - Rimerman,Ronald A, AU - Scammell,Jonathan G, AU - Smith,David F, AU - Clardy,Jon, Y1 - 2003/01/21/ PY - 2003/1/23/pubmed PY - 2003/3/19/medline PY - 2003/1/23/entrez SP - 868 EP - 73 JF - Proceedings of the National Academy of Sciences of the United States of America JO - Proc Natl Acad Sci U S A VL - 100 IS - 3 N2 - The ability to bind immunosuppressive drugs such as cyclosporin and FK506 defines the immunophilin family of proteins, and the FK506-binding proteins form the FKBP subfamily of immunophilins. Some FKBPs, notably FKBP12 (the 12-kDa FK506-binding protein), have defined roles in regulating ion channels or cell signaling, and well established structures. Other FKBPs, especially the larger ones, participate in important biological processes, but their exact roles and the structural bases for these roles are poorly defined. FKBP51 (the 51-kDa FKBP) associates with heat shock protein 90 (Hsp90) and appears in functionally mature steroid receptor complexes. In New World monkeys, FKBP51 has been implicated in cortisol resistance. We report here the x-ray structures of human FKBP51, to 2.7 A, and squirrel monkey FKBP51, to 2.8 A, by using multiwavelength anomalous dispersion phasing. FKBP51 is composed of three domains: two consecutive FKBP domains and a three-unit repeat of the TPR (tetratricopeptide repeat) domain. This structure of a multi-FKBP domain protein clarifies the arrangement of these domains and their possible interactions with other proteins. The two FKBP domains differ by an insertion in the second that affects the formation of the progesterone receptor complex. SN - 0027-8424 UR - https://www.unboundmedicine.com/medline/citation/12538866/Structure_of_the_large_FK506_binding_protein_FKBP51_an_Hsp90_binding_protein_and_a_component_of_steroid_receptor_complexes_ L2 - http://www.pnas.org/cgi/pmidlookup?view=long&pmid=12538866 DB - PRIME DP - Unbound Medicine ER -