View source for 6d14


==Zebrafish TRAP1 bound to AMPPNP and calcium in the asymmetric closed state==
<StructureSection load='6d14' size='340' side='right'caption='[[6d14]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6d14]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Danio_rerio Danio rerio]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6D14 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6D14 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]] 2.5&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ANP:PHOSPHOAMINOPHOSPHONIC+ACID-ADENYLATE+ESTER'>ANP</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene></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=6d14 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6d14 OCA], [https://pdbe.org/6d14 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6d14 RCSB], [https://www.ebi.ac.uk/pdbsum/6d14 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6d14 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/A8WFV1_DANRE A8WFV1_DANRE] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The Hsp90 molecular chaperones are ATP-dependent enzymes that maintain protein homeostasis and regulate many essential cellular processes. Higher eukaryotes have organelle-specific Hsp90 paralogs that are adapted to each subcellular environment. The mitochondrial Hsp90, TNF receptor-associated protein 1 (TRAP1), supports the folding and activity of electron transport components and is increasingly appreciated as a critical player in mitochondrial signaling. Calcium plays a well-known and important regulatory role in mitochondria where it can accumulate to much higher concentrations than in the cytoplasm. Surprisingly, we found here that calcium can replace magnesium, the essential enzymatic cofactor, to support TRAP1 ATPase activity. Anomalous X-ray diffraction experiments revealed a calcium-binding site within the TRAP1 nucleotide-binding pocket located near the ATP alpha-phosphate and completely distinct from the magnesium-binding site adjacent to the beta- and gamma-phosphates. In the presence of magnesium, ATP hydrolysis by TRAP1, as with other Hsp90s, was noncooperative, whereas calcium binding resulted in cooperative hydrolysis by the two protomers within the Hsp90 dimer. The structural data suggested a mechanism for this cooperative behavior. Because of the cooperativity, at high ATP concentrations, ATPase activity was higher with calcium, whereas the converse was observed at low ATP concentrations. Integrating these observations, we propose a model in which the divalent cation choice can control switching between noncooperative and cooperative TRAP1 ATPase mechanisms in response to varying ATP concentrations. This switching may facilitate coordination between cellular energetics, mitochondrial signaling, and protein homeostasis via alterations in the TRAP1 ATP-driven cycle and its consequent effects on different mitochondrial clients.

Calcium binding to a remote site can replace magnesium as cofactor for mitochondrial Hsp90 (TRAP1) ATPase activity.,Elnatan D, Agard DA J Biol Chem. 2018 Aug 31;293(35):13717-13724. doi: 10.1074/jbc.RA118.003562. Epub, 2018 Jul 10. PMID:29991590<ref>PMID:29991590</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6d14" style="background-color:#fffaf0;"></div>
== References ==
<references/>
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</StructureSection>
[[Category: Danio rerio]]
[[Category: Large Structures]]
[[Category: Agard DA]]
[[Category: Elnatan D]]