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2mgy

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Revision as of 06:35, 2 March 2023

Solution structure of the mitochondrial translocator protein (TSPO) in complex with its high-affinity ligand PK11195

Structural highlights

2mgy is a 1 chain structure with sequence from Mus musculus. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

TSPO_MOUSE Can bind protoporphyrin IX and may play a role in the transport of porphyrins and heme (By similarity). Was initially identified as peripheral-type benzodiazepine receptor; can also bind isoquinoline carboxamides. Promotes the transport of cholesterol across mitochondrial membranes and may play a role in lipid metabolism (PubMed:9832438, PubMed:24814875), but its precise physiological role is controversial. According to some reports, it is not required for steroid hormone biosynthesis (PubMed:24174323, PubMed:24936060).^[1] ^[2] ^[3] ^[4] ^[5]

Publication Abstract from PubMed

The 18-kilodalton translocator protein TSPO is found in mitochondrial membranes and mediates the import of cholesterol and porphyrins into mitochondria. In line with the role of TSPO in mitochondrial function, TSPO ligands are used for a variety of diagnostic and therapeutic applications in animals and humans. We present the three-dimensional high-resolution structure of mammalian TSPO reconstituted in detergent micelles in complex with its high-affinity ligand PK11195. The TSPO-PK11195 structure is described by a tight bundle of five transmembrane alpha helices that form a hydrophobic pocket accepting PK11195. Ligand-induced stabilization of the structure of TSPO suggests a molecular mechanism for the stimulation of cholesterol transport into mitochondria.

Structure of the mitochondrial translocator protein in complex with a diagnostic ligand.,Jaremko L, Jaremko M, Giller K, Becker S, Zweckstetter M Science. 2014 Mar 21;343(6177):1363-6. doi: 10.1126/science.1248725. PMID:24653034^[6]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Morohaku K, Pelton SH, Daugherty DJ, Butler WR, Deng W, Selvaraj V. Translocator protein/peripheral benzodiazepine receptor is not required for steroid hormone biosynthesis. Endocrinology. 2014 Jan;155(1):89-97. PMID:24174323 doi:10.1210/en.2013-1556
↑ Taylor JM, Allen AM, Graham A. Targeting mitochondrial 18 kDa translocator protein (TSPO) regulates macrophage cholesterol efflux and lipid phenotype. Clin Sci (Lond). 2014 Nov;127(10):603-13. PMID:24814875 doi:10.1042/CS20140047
↑ Tu LN, Morohaku K, Manna PR, Pelton SH, Butler WR, Stocco DM, Selvaraj V. Peripheral benzodiazepine receptor/translocator protein global knock-out mice are viable with no effects on steroid hormone biosynthesis. J Biol Chem. 2014 Oct 3;289(40):27444-54. PMID:24936060 doi:10.1074/jbc.M114.578286
↑ Garnier M, Dimchev AB, Boujrad N, Price JM, Musto NA, Papadopoulos V. In vitro reconstitution of a functional peripheral-type benzodiazepine receptor from mouse Leydig tumor cells. Mol Pharmacol. 1994 Feb;45(2):201-11 PMID:8114671
↑ Li H, Papadopoulos V. Peripheral-type benzodiazepine receptor function in cholesterol transport. Identification of a putative cholesterol recognition/interaction amino acid sequence and consensus pattern. Endocrinology. 1998 Dec;139(12):4991-7. PMID:9832438 doi:10.1210/endo.139.12.6390
↑ Jaremko L, Jaremko M, Giller K, Becker S, Zweckstetter M. Structure of the mitochondrial translocator protein in complex with a diagnostic ligand. Science. 2014 Mar 21;343(6177):1363-6. doi: 10.1126/science.1248725. PMID:24653034 doi:http://dx.doi.org/10.1126/science.1248725

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2mgy"

@@ Line 1: / Line 1: @@
 ==Solution structure of the mitochondrial translocator protein (TSPO) in complex with its high-affinity ligand PK11195==
-<StructureSection load='2mgy' size='340' side='right'caption='[[2mgy]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''>
+<StructureSection load='2mgy' size='340' side='right'caption='[[2mgy]]' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[2mgy]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2MGY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2MGY FirstGlance]. <br>
+<table><tr><td colspan='2'>[[2mgy]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2MGY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2MGY FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PKA:N-[(2R)-BUTAN-2-YL]-1-(2-CHLOROPHENYL)-N-METHYLISOQUINOLINE-3-CARBOXAMIDE'>PKA</scene></td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Tspo, Bzrp ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</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=2mgy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2mgy OCA], [https://pdbe.org/2mgy PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2mgy RCSB], [https://www.ebi.ac.uk/pdbsum/2mgy PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2mgy ProSAT]</span></td></tr>
 </table>
+== Function ==
+[https://www.uniprot.org/uniprot/TSPO_MOUSE TSPO_MOUSE] Can bind protoporphyrin IX and may play a role in the transport of porphyrins and heme (By similarity). Was initially identified as peripheral-type benzodiazepine receptor; can also bind isoquinoline carboxamides. Promotes the transport of cholesterol across mitochondrial membranes and may play a role in lipid metabolism (PubMed:9832438, PubMed:24814875), but its precise physiological role is controversial. According to some reports, it is not required for steroid hormone biosynthesis (PubMed:24174323, PubMed:24936060).<ref>PMID:24174323</ref> <ref>PMID:24814875</ref> <ref>PMID:24936060</ref> <ref>PMID:8114671</ref> <ref>PMID:9832438</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 22: / Line 23: @@
 </StructureSection>
 [[Category: Large Structures]]
-[[Category: Lk3 transgenic mice]]
+[[Category: Mus musculus]]
-[[Category: Becker, S]]
+[[Category: Becker S]]
-[[Category: Giller, K]]
+[[Category: Giller K]]
-[[Category: Jaremko, L]]
+[[Category: Jaremko L]]
-[[Category: Jaremko, M]]
+[[Category: Jaremko M]]
-[[Category: Zweckstetter, M]]
+[[Category: Zweckstetter M]]
-[[Category: Dpc micelle]]
-[[Category: Helical membrane channel protein]]
-[[Category: Membrane protein]]
-[[Category: Mitochondrial membrane]]
-[[Category: Peripheral benzodiazepine receptor]]
-[[Category: Pk11195]]
-[[Category: Protein-ligand complex]]

2mgy

From Proteopedia

Revision as of 06:35, 2 March 2023

Solution structure of the mitochondrial translocator protein (TSPO) in complex with its high-affinity ligand PK11195

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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