4lax

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Revision as of 07:33, 4 August 2016

Crystal Structure Analysis of FKBP52, Complex with FK506

Structural highlights

4lax is a 1 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, ,
Related:	1q1c, 4lav, 4law, 4lay
Gene:	FKBP4, FKBP52 (HUMAN)
Activity:	Peptidylprolyl isomerase, with EC number 5.2.1.8
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[FKBP4_HUMAN] Immunophilin protein with PPIase and co-chaperone activities (By similarity). Component of unligated steroid receptors heterocomplexes through interaction with heat-shock protein 90 (HSP90). May play a role in the intracellular trafficking of heterooligomeric forms of steroid hormone receptors between cytoplasm and nuclear compartments (By similarity). The isomerase activity controls neuronal growth cones via regulation of TRPC1 channel opening. Acts also as a regulator of microtubule dynamics by inhibiting MAPT/TAU ability to promote microtubule assembly. May have a protective role against oxidative stress in mitochondria.^[1] ^[2] ^[3] ^[4] ^[5]

Publication Abstract from PubMed

The human Hsp90 co-chaperone FKBP52 belongs to the family of FK506-binding proteins, which act as peptidyl-prolyl isomerases. FKBP52 specifically enhances the signaling of steroid hormone receptors, modulates ion channels and regulates neuronal outgrowth dynamics. In turn, small-molecule ligands of FKBP52 have been suggested as potential neurotrophic or anti-prostate cancer agents. The usefulness of available ligands is however limited by a lack of selectivity. The immunophilin FKBP52 is composed of three domains, an FK506-binding domain with peptidyl-prolyl isomerase activity, an FKBP-like domain of unknown function and a TPR-clamp domain, which recognizes the C-terminal peptide of Hsp90 with high affinity. The herein reported crystal structures of FKBP52 reveal that the short linker connecting the FK506-binding domain and the FKBP-like domain acts as a flexible hinge. This enhanced flexibility and its modulation by phosphorylation might explain some of the functional antagonism between the closely related homologs FKBP51 and FKBP52. We further present two co-crystal structures of FKBP52 in complex with the prototypic ligand FK506 and a synthetic analog thereof. These structures revealed the molecular interactions in great detail, which enabled in-depth comparison with the corresponding complexes of the other cytosolic FKBPs, FKBP51 and FKBP12. The observed subtle differences provide crucial insights for the rational design of ligands with improved selectivity for FKBP52.

Crystal Structures of the Free and Ligand-Bound FK1-FK2 Domain Segment of FKBP52 Reveal a Flexible Inter-Domain Hinge.,Bracher A, Kozany C, Hahle A, Wild P, Zacharias M, Hausch F J Mol Biol. 2013 Aug 8. pii: S0022-2836(13)00502-0. doi:, 10.1016/j.jmb.2013.07.041. PMID:23933011^[6]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Peattie DA, Harding MW, Fleming MA, DeCenzo MT, Lippke JA, Livingston DJ, Benasutti M. Expression and characterization of human FKBP52, an immunophilin that associates with the 90-kDa heat shock protein and is a component of steroid receptor complexes. Proc Natl Acad Sci U S A. 1992 Nov 15;89(22):10974-8. PMID:1279700
↑ Tai PK, Albers MW, Chang H, Faber LE, Schreiber SL. Association of a 59-kilodalton immunophilin with the glucocorticoid receptor complex. Science. 1992 May 29;256(5061):1315-8. PMID:1376003
↑ Sanchez ER, Faber LE, Henzel WJ, Pratt WB. The 56-59-kilodalton protein identified in untransformed steroid receptor complexes is a unique protein that exists in cytosol in a complex with both the 70- and 90-kilodalton heat shock proteins. Biochemistry. 1990 May 29;29(21):5145-52. PMID:2378870
↑ Shim S, Yuan JP, Kim JY, Zeng W, Huang G, Milshteyn A, Kern D, Muallem S, Ming GL, Worley PF. Peptidyl-prolyl isomerase FKBP52 controls chemotropic guidance of neuronal growth cones via regulation of TRPC1 channel opening. Neuron. 2009 Nov 25;64(4):471-83. doi: 10.1016/j.neuron.2009.09.025. PMID:19945390 doi:10.1016/j.neuron.2009.09.025
↑ Gallo LI, Lagadari M, Piwien-Pilipuk G, Galigniana MD. The 90-kDa heat-shock protein (Hsp90)-binding immunophilin FKBP51 is a mitochondrial protein that translocates to the nucleus to protect cells against oxidative stress. J Biol Chem. 2011 Aug 26;286(34):30152-60. doi: 10.1074/jbc.M111.256610. Epub, 2011 Jul 5. PMID:21730050 doi:10.1074/jbc.M111.256610
↑ Bracher A, Kozany C, Hahle A, Wild P, Zacharias M, Hausch F. Crystal Structures of the Free and Ligand-Bound FK1-FK2 Domain Segment of FKBP52 Reveal a Flexible Inter-Domain Hinge. J Mol Biol. 2013 Aug 8. pii: S0022-2836(13)00502-0. doi:, 10.1016/j.jmb.2013.07.041. PMID:23933011 doi:10.1016/j.jmb.2013.07.041

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4lax"

@@ Line 1: / Line 1: @@
 ==Crystal Structure Analysis of FKBP52, Complex with FK506==
 <StructureSection load='4lax' size='340' side='right' caption='[[4lax]], [[Resolution|resolution]] 2.01&Aring;' scene=''>
@@ Line 7: / Line 8: @@
 <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">FKBP4, FKBP52 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
 <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Peptidylprolyl_isomerase Peptidylprolyl isomerase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=5.2.1.8 5.2.1.8] </span></td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4lax FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4lax OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4lax RCSB], [http://www.ebi.ac.uk/pdbsum/4lax PDBsum]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4lax FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4lax OCA], [http://pdbe.org/4lax PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4lax RCSB], [http://www.ebi.ac.uk/pdbsum/4lax PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4lax ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 19: / Line 20: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 4lax" style="background-color:#fffaf0;"></div>
 ==See Also==

4lax

From Proteopedia

Revision as of 07:33, 4 August 2016

Crystal Structure Analysis of FKBP52, Complex with FK506

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

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