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4aif

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==AIP TPR domain in complex with human Hsp90 peptide==
==AIP TPR domain in complex with human Hsp90 peptide==
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<StructureSection load='4aif' size='340' side='right' caption='[[4aif]], [[Resolution|resolution]] 2.01&Aring;' scene=''>
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<StructureSection load='4aif' size='340' side='right'caption='[[4aif]], [[Resolution|resolution]] 2.01&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[4aif]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4AIF OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4AIF FirstGlance]. <br>
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<table><tr><td colspan='2'>[[4aif]] is a 4 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=4AIF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4AIF FirstGlance]. <br>
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
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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]] 2.006&#8491;</td></tr>
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<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1byq|1byq]], [[1osf|1osf]], [[1uy6|1uy6]], [[1uy7|1uy7]], [[1uy8|1uy8]], [[1uy9|1uy9]], [[1uyc|1uyc]], [[1uyd|1uyd]], [[1uye|1uye]], [[1uyf|1uyf]], [[1uyg|1uyg]], [[1uyh|1uyh]], [[1uyi|1uyi]], [[1uyk|1uyk]], [[1uyl|1uyl]], [[1yc1|1yc1]], [[1yc3|1yc3]], [[1yc4|1yc4]], [[1yer|1yer]], [[1yes|1yes]], [[1yet|1yet]], [[2bsm|2bsm]], [[2bt0|2bt0]], [[2bug|2bug]], [[2byh|2byh]], [[2byi|2byi]], [[2bz5|2bz5]], [[2c2l|2c2l]], [[2ccs|2ccs]], [[2cct|2cct]], [[2ccu|2ccu]], [[2cdd|2cdd]], [[2fwy|2fwy]], [[2fwz|2fwz]], [[2jjc|2jjc]], [[2uwd|2uwd]], [[2vci|2vci]], [[2vcj|2vcj]], [[2wi1|2wi1]], [[2wi2|2wi2]], [[2wi3|2wi3]], [[2wi4|2wi4]], [[2wi5|2wi5]], [[2wi6|2wi6]], [[2wi7|2wi7]], [[2xab|2xab]], [[2xdk|2xdk]], [[2xdl|2xdl]], [[2xds|2xds]], [[2xdu|2xdu]], [[2xdx|2xdx]], [[2xhr|2xhr]], [[2xht|2xht]], [[2xhx|2xhx]], [[2xjg|2xjg]], [[2xjj|2xjj]], [[2xjx|2xjx]], [[2xk2|2xk2]], [[2ye2|2ye2]], [[2ye3|2ye3]], [[2ye4|2ye4]], [[2ye5|2ye5]], [[2ye6|2ye6]], [[2ye7|2ye7]], [[2ye8|2ye8]], [[2ye9|2ye9]], [[2yea|2yea]], [[2yeb|2yeb]], [[2yec|2yec]], [[2yed|2yed]], [[2yee|2yee]], [[2yef|2yef]], [[2yeg|2yeg]], [[2yeh|2yeh]], [[2yei|2yei]], [[2yej|2yej]], [[2yi0|2yi0]], [[2yi5|2yi5]], [[2yi6|2yi6]], [[2yi7|2yi7]], [[2yjw|2yjw]], [[2yjx|2yjx]], [[2yk2|2yk2]], [[2yk9|2yk9]], [[2ykb|2ykb]], [[2ykc|2ykc]], [[2yke|2yke]], [[2yki|2yki]], [[2ykj|2ykj]]</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=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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4aif FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4aif OCA], [http://pdbe.org/4aif PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4aif RCSB], [http://www.ebi.ac.uk/pdbsum/4aif PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4aif ProSAT]</span></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=4aif FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4aif OCA], [https://pdbe.org/4aif PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4aif RCSB], [https://www.ebi.ac.uk/pdbsum/4aif PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4aif ProSAT]</span></td></tr>
</table>
</table>
== Disease ==
== Disease ==
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[[http://www.uniprot.org/uniprot/AIP_HUMAN AIP_HUMAN]] Acromegaly;Familial prolactinoma. Defects in AIP are a cause of growth hormone-secreting pituitary adenoma (GHSPA) [MIM:[http://omim.org/entry/102200 102200]]; also known as familial isolated somatotropinomas (FIS) or isolated familial somatotropinoma (IFS) or familial somatotrophinoma or acromegaly due to pituitary adenoma.<ref>PMID:17244780</ref> <ref>PMID:17299063</ref> <ref>PMID:17360484</ref> <ref>PMID:18410548</ref> Defects in AIP are a cause of ACTH-secreting pituitary adenoma (ASPA) [MIM:[http://omim.org/entry/219090 219090]]; also known as pituitary Cushing disease. A pituary adenoma resulting in excessive production of adrenocorticotropic hormone. This leads to hypersecretion of cortisol by the adrenal glands and ACTH-dependent Cushing syndrome. Clinical manifestations of Cushing syndrome include facial and trunkal obesity, abdominal striae, muscular weakness, osteoporosis, arterial hypertension, diabetes. Defects in AIP are a cause of prolactin-secreting pituitary adenoma (PSPA) [MIM:[http://omim.org/entry/600634 600634]]; also known as prolactinoma. Prolactin-secreting pituitary adenoma is the most common type of hormonally active pituitary adenoma.
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[https://www.uniprot.org/uniprot/AIP_HUMAN AIP_HUMAN] Acromegaly;Familial prolactinoma. Defects in AIP are a cause of growth hormone-secreting pituitary adenoma (GHSPA) [MIM:[https://omim.org/entry/102200 102200]; also known as familial isolated somatotropinomas (FIS) or isolated familial somatotropinoma (IFS) or familial somatotrophinoma or acromegaly due to pituitary adenoma.<ref>PMID:17244780</ref> <ref>PMID:17299063</ref> <ref>PMID:17360484</ref> <ref>PMID:18410548</ref> Defects in AIP are a cause of ACTH-secreting pituitary adenoma (ASPA) [MIM:[https://omim.org/entry/219090 219090]; also known as pituitary Cushing disease. A pituary adenoma resulting in excessive production of adrenocorticotropic hormone. This leads to hypersecretion of cortisol by the adrenal glands and ACTH-dependent Cushing syndrome. Clinical manifestations of Cushing syndrome include facial and trunkal obesity, abdominal striae, muscular weakness, osteoporosis, arterial hypertension, diabetes. Defects in AIP are a cause of prolactin-secreting pituitary adenoma (PSPA) [MIM:[https://omim.org/entry/600634 600634]; also known as prolactinoma. Prolactin-secreting pituitary adenoma is the most common type of hormonally active pituitary adenoma.
== Function ==
== Function ==
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[[http://www.uniprot.org/uniprot/AIP_HUMAN AIP_HUMAN]] May play a positive role in AHR-mediated (aromatic hydrocarbon receptor) signaling, possibly by influencing its receptivity for ligand and/or its nuclear targeting. Cellular negative regulator of the hepatitis B virus (HBV) X protein. [[http://www.uniprot.org/uniprot/HS90A_HUMAN HS90A_HUMAN]] Molecular chaperone that promotes the maturation, structural maintenance and proper regulation of specific target proteins involved for instance in cell cycle control and signal transduction. Undergoes a functional cycle that is linked to its ATPase activity. This cycle probably induces conformational changes in the client proteins, thereby causing their activation. Interacts dynamically with various co-chaperones that modulate its substrate recognition, ATPase cycle and chaperone function.<ref>PMID:15937123</ref> <ref>PMID:11274138</ref>
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[https://www.uniprot.org/uniprot/AIP_HUMAN AIP_HUMAN] May play a positive role in AHR-mediated (aromatic hydrocarbon receptor) signaling, possibly by influencing its receptivity for ligand and/or its nuclear targeting. Cellular negative regulator of the hepatitis B virus (HBV) X protein.
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Mutations of the aryl hydrocarbon receptor interacting protein (AIP) have been associated with familial isolated pituitary adenomas predisposing to young-onset acromegaly and gigantism. The precise tumorigenic mechanism is not well understood as AIP interacts with a large number of independent proteins as well as three chaperone systems, HSP90, HSP70 and TOMM20. We have determined the structure of the TPR domain of AIP at high resolution, which has allowed a detailed analysis of how disease-associated mutations impact on the structural integrity of the TPR domain. A subset of C-terminal alpha-7 helix (Calpha-7h) mutations, R304* (nonsense mutation), R304Q, Q307* and R325Q, a known site for AhR and PDE4A5 client-protein interaction, occur beyond those that interact with the conserved MEEVD and EDDVE sequences of HSP90 and TOMM20. These C-terminal AIP mutations appear to only disrupt client-protein binding to the Calpha-7h, while chaperone binding remains unaffected, suggesting that failure of client-protein interaction with the Calpha-7h is sufficient to predispose to pituitary adenoma. We have also identified a molecular switch in the AIP TPR-domain that allows recognition of both the conserved HSP90 motif, MEEVD, and the equivalent sequence (EDDVE) of TOMM20.
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Structure of the TPR Domain of AIP: Lack of Client Protein Interaction with the C-Terminal alpha-7 Helix of the TPR Domain of AIP Is Sufficient for Pituitary Adenoma Predisposition.,Morgan RM, Hernandez-Ramirez LC, Trivellin G, Zhou L, Roe SM, Korbonits M, Prodromou C PLoS One. 2012;7(12):e53339. doi: 10.1371/journal.pone.0053339. Epub 2012 Dec 31. PMID:23300914<ref>PMID:23300914</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 4aif" style="background-color:#fffaf0;"></div>
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== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
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[[Category: Human]]
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[[Category: Homo sapiens]]
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[[Category: Morgan, R M.L]]
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[[Category: Large Structures]]
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[[Category: Pearl, L H]]
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[[Category: Morgan RML]]
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[[Category: Prodromou, C]]
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[[Category: Pearl LH]]
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[[Category: Roe, S M]]
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[[Category: Prodromou C]]
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[[Category: Aryl hydrocarbon receptor]]
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[[Category: Roe SM]]
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[[Category: Signaling protein-peptide complex]]
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Current revision

AIP TPR domain in complex with human Hsp90 peptide

PDB ID 4aif

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