4drj

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{{STRUCTURE_4drj| PDB=4drj | SCENE= }}
 
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===o-crystal structure of the PPIase domain of FKBP52, Rapamycin and the FRB fragment of mTOR===
 
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{{ABSTRACT_PUBMED_23358420}}
 
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==Function==
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==o-crystal structure of the PPIase domain of FKBP52, Rapamycin and the FRB fragment of mTOR==
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[[http://www.uniprot.org/uniprot/FKBP4_HUMAN 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.<ref>PMID:1279700</ref><ref>PMID:1376003</ref><ref>PMID:2378870</ref><ref>PMID:19945390</ref><ref>PMID:21730050</ref> [[http://www.uniprot.org/uniprot/MTOR_HUMAN MTOR_HUMAN]] Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals. Functions as part of 2 structurally and functionally distinct signaling complexes mTORC1 and mTORC2 (mTOR complex 1 and 2). Activated mTORC1 up-regulates protein synthesis by phosphorylating key regulators of mRNA translation and ribosome synthesis. This includes phosphorylation of EIF4EBP1 and release of its inhibition toward the elongation initiation factor 4E (eiF4E). Moreover, phosphorylates and activates RPS6KB1 and RPS6KB2 that promote protein synthesis by modulating the activity of their downstream targets including ribosomal protein S6, eukaryotic translation initiation factor EIF4B and the inhibitor of translation initiation PDCD4. Regulates ribosome synthesis by activating RNA polymerase III-dependent transcription through phosphorylation and inhibition of MAF1 a RNA polymerase III-repressor. In parallel to protein synthesis, also regulates lipid synthesis through SREBF1/SREBP1 and LPIN1. To maintain energy homeostasis mTORC1 may also regulate mitochondrial biogenesis through regulation of PPARGC1A. mTORC1 also negatively regulates autophagy through phosphorylation of ULK1. Under nutrient sufficiency, phosphorylates ULK1 at 'Ser-758', disrupting the interaction with AMPK and preventing activation of ULK1. Also prevents autophagy through phosphorylation of the autophagy inhibitor DAP. mTORC1 exerts a feedback control on upstream growth factor signaling that includes phosphorylation and activation of GRB10 a INSR-dependent signaling suppressor. Among other potential targets mTORC1 may phosphorylate CLIP1 and regulate microtubules. As part of the mTORC2 complex MTOR may regulate other cellular processes including survival and organization of the cytoskeleton. Plays a critical role in the phosphorylation at 'Ser-473' of AKT1, a pro-survival effector of phosphoinositide 3-kinase, facilitating its activation by PDK1. mTORC2 may regulate the actin cytoskeleton, through phosphorylation of PRKCA, PXN and activation of the Rho-type guanine nucleotide exchange factors RHOA and RAC1A or RAC1B. mTORC2 also regulates the phosphorylation of SGK1 at 'Ser-422'.<ref>PMID:12150925</ref><ref>PMID:12150926</ref><ref>PMID:12231510</ref><ref>PMID:12087098</ref><ref>PMID:14651849</ref><ref>PMID:12718876</ref><ref>PMID:15268862</ref><ref>PMID:15545625</ref><ref>PMID:15467718</ref><ref>PMID:15718470</ref><ref>PMID:18925875</ref><ref>PMID:18762023</ref><ref>PMID:18497260</ref><ref>PMID:20537536</ref><ref>PMID:20516213</ref><ref>PMID:21659604</ref>
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<StructureSection load='4drj' size='340' side='right'caption='[[4drj]], [[Resolution|resolution]] 1.80&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[4drj]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4DRJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4DRJ FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.8&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=RAP:RAPAMYCIN+IMMUNOSUPPRESSANT+DRUG'>RAP</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4drj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4drj OCA], [https://pdbe.org/4drj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4drj RCSB], [https://www.ebi.ac.uk/pdbsum/4drj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4drj ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/FKBP4_HUMAN 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.<ref>PMID:1279700</ref> <ref>PMID:1376003</ref> <ref>PMID:2378870</ref> <ref>PMID:19945390</ref> <ref>PMID:21730050</ref>
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==About this Structure==
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==See Also==
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[[4drj]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4DRJ OCA].
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*[[FKBP 3D structures|FKBP 3D structures]]
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*[[Serine/threonine protein kinase 3D structures|Serine/threonine protein kinase 3D structures]]
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==Reference==
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== References ==
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<references group="xtra"/><references/>
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<references/>
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__TOC__
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Peptidylprolyl isomerase]]
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[[Category: Large Structures]]
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[[Category: Bracher, A.]]
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[[Category: Bracher A]]
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[[Category: Hausch, F.]]
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[[Category: Hausch F]]
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[[Category: Maerz, A M.]]
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[[Category: Maerz AM]]
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[[Category: Cancer]]
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[[Category: Fk-506 binding domain]]
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[[Category: Hsp90 cochaperone]]
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[[Category: Immunophilin]]
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[[Category: Immunosuppression]]
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[[Category: Isomerase-transferase complex]]
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[[Category: Kinase]]
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[[Category: Mammalian target of rapamycin]]
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[[Category: Peptidyl-prolyl isomerase]]
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[[Category: Signalling]]
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Current revision

o-crystal structure of the PPIase domain of FKBP52, Rapamycin and the FRB fragment of mTOR

PDB ID 4drj

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Proteopedia Page Contributors and Editors (what is this?)

OCA

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