4r0x

Allosteric coupling of conformational transitions in the FK1 domain of FKBP51 near the site of steroid receptor interaction

spinqualitylabelsall models 4r0x, resolution 1.20Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4r0x is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.2Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function FKBP5_HUMAN Interacts with functionally mature heterooligomeric progesterone receptor complexes along with HSP90 and TEBP. Publication Abstract from PubMed Interchanging Leu 119 for Pro 119 at the tip of the beta4-beta5 loop in the first FK506 binding domain (FK1) of the FKBP51 and FKBP52 proteins, respectively, has been reported to largely reverse the inhibitory (FKBP51) or stimulatory (FKBP52) effects of these cochaperones on the transcriptional activity of glucocorticoid and androgen receptor protein complexes. Previous NMR relaxation studies have identified exchange linebroadening, indicative of submillisecond conformational motion, throughout the beta4-beta5 loop in the FK1 domain of FKBP51 which are suppressed by the FKBP52-like L119P substitution. This substitution also attenuates exchange linebroadening in the underlying beta2 and beta3a strands that is centered near a bifurcated mainchain hydrogen bond interaction between these two strands. The present study demonstrates that these exchange linebroadening effects arise from two distinct coupled conformational transitions, and the transition within the beta2 and beta3a strands samples a transient conformation which resembles the crystal structures of the selectively-inhibited FK1 domain of FKBP51 recently reported by Hausch and colleagues. Although the crystal structures for their series of inhibitors were interpreted as evidence for an induced fit mechanism of association, the presence of a similar conformation being significantly populated in the unliganded FKBP51 domain is more consistent with a conformational selection binding process. The contrastingly reduced conformational plasticity of the corresponding FK1 domain of FKBP52 is consistent with the current model in which FKBP51 binds to both the apo- and hormone-bound forms of the steroid receptor to modulate its affinity for ligand, while FKBP52 binds selectively to the latter state. Coupling of conformational transitions in the N-terminal domain of the 51 kDa FK506-binding protein (FKBP51) near its site of interaction with the steroid receptor proteins.,LeMaster DM, Mustafi SM, Brecher M, Zhang J, Heroux A, Li H, Hernandez G J Biol Chem. 2015 May 7. pii: jbc.M115.650655. PMID:25953903 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also FKBP 3D structures

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