View source for 6iqe


==Human prohibitin 2==
<StructureSection load='6iqe' size='340' side='right'caption='[[6iqe]], [[Resolution|resolution]] 1.70&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6iqe]] is a 1 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=6IQE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6IQE FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.701&#8491;</td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6iqe FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6iqe OCA], [https://pdbe.org/6iqe PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6iqe RCSB], [https://www.ebi.ac.uk/pdbsum/6iqe PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6iqe ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/PHB2_HUMAN PHB2_HUMAN] Protein with pleiotropic attributes mediated in a cell-compartment- and tissue-specific manner, which include the plasma membrane-associated cell signaling functions, mitochondrial chaperone, and transcriptional co-regulator of transcription factors and sex steroid hormones in the nucleus.<ref>PMID:10359819</ref> <ref>PMID:11302691</ref> <ref>PMID:20959514</ref> <ref>PMID:24003225</ref> <ref>PMID:28017329</ref> <ref>PMID:31522117</ref>   In the mitochondria, together with PHB, forms large ring complexes (prohibitin complexes) in the inner mitochondrial membrane (IMM) and functions as chaperone protein that stabilizes mitochondrial respiratory enzymes and maintains mitochondrial integrity in the IMM, which is required for mitochondrial morphogenesis, neuronal survival, and normal lifespan (Probable). The prohibitin complex, with DNAJC19, regulates cardiolipin remodeling and the protein turnover of OMA1 in a cardiolipin-binding manner (By similarity). Also regulates cytochrome-c oxidase assembly (COX) and mitochondrial respiration (PubMed:20959514, PubMed:11302691). Binding to sphingoid 1-phosphate (SPP) modulates its regulator activity (PubMed:20959514, PubMed:11302691). Has a key role of mitophagy receptor involved in targeting mitochondria for autophagic degradation (PubMed:28017329). Involved in mitochondrial-mediated antiviral innate immunity, activates RIG-I-mediated signal transduction and production of IFNB1 and pro-inflammatory cytokine IL6 (PubMed:31522117).[UniProtKB:O35129]<ref>PMID:11302691</ref> <ref>PMID:20959514</ref> <ref>PMID:28017329</ref> <ref>PMID:31522117</ref> <ref>PMID:25904163</ref>   In the nucleus, serves as transcriptional co-regulator (Probable). Acts as a mediator of transcriptional repression by nuclear hormone receptors via recruitment of histone deacetylases. Functions as an estrogen receptor (ER)-selective coregulator that potentiates the inhibitory activities of antiestrogens and represses the activity of estrogens. Competes with NCOA1 for modulation of ER transcriptional activity (By similarity).[UniProtKB:O35129]<ref>PMID:25904163</ref>   In the plasma membrane, is involved in IGFBP6-induced cell migration (PubMed:24003225). Cooperates with CD86 to mediate CD86-signaling in B lymphocytes that regulates the level of IgG1 produced through the activation of distal signaling intermediates. Upon CD40 engagement, required to activate NF-kappa-B signaling pathway via phospholipase C and protein kinase C activation (By similarity).[UniProtKB:O35129]<ref>PMID:24003225</ref>   (Microbial infection) Involved in human enterovirus 71/EV-71 infection by enhancing the autophagy mechanism during the infection.<ref>PMID:32276428</ref> 
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== Publication Abstract from PubMed ==
The coiled-coil motif mediates subunit oligomerization and scaffolding and underlies several fundamental biologic processes. Prohibitins (PHBs), mitochondrial inner membrane proteins involved in mitochondrial homeostasis and signal transduction, are predicted to have a coiled-coil motif, but their structural features are poorly understood. Here we solved the crystal structure of the heptad repeat (HR) region of PHB2 at 1.7-A resolution, showing that it assembles into a dimeric, antiparallel coiled-coil with a unique negatively charged area essential for the PHB interactome in mitochondria. Disruption of the HR coiled-coil abolishes well-ordered PHB complexes and the mitochondrial tubular networks accompanying PHB-dependent signaling. Using a proximity-dependent biotin identification (BioID) technique in live cells, we mapped a number of mitochondrial intermembrane space proteins whose association with PHB2 relies on the HR coiled-coil region. Elucidation of the PHB complex structure in mitochondria provides insight into essential PHB interactomes required for mitochondrial dynamics as well as signal transduction.

Structural Basis of Mitochondrial Scaffolds by Prohibitin Complexes: Insight into a Role of the Coiled-Coil Region.,Yoshinaka T, Kosako H, Yoshizumi T, Furukawa R, Hirano Y, Kuge O, Tamada T, Koshiba T iScience. 2019 Sep 27;19:1065-1078. doi: 10.1016/j.isci.2019.08.056. Epub 2019, Sep 3. PMID:31522117<ref>PMID:31522117</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 6iqe" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Hirano Y]]
[[Category: Koshiba T]]
[[Category: Tamada T]]