7dny
From Proteopedia
(Difference between revisions)
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== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[7dny]] 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=7DNY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7DNY FirstGlance]. <br> | <table><tr><td colspan='2'>[[7dny]] 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=7DNY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7DNY FirstGlance]. <br> | ||
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=HT9:coproporphyrin+III'>HT9</scene>, <scene name='pdbligand=Y01:CHOLESTEROL+HEMISUCCINATE'>Y01</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.4Å</td></tr> |
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=HT9:coproporphyrin+III'>HT9</scene>, <scene name='pdbligand=Y01:CHOLESTEROL+HEMISUCCINATE'>Y01</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=7dny FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7dny OCA], [https://pdbe.org/7dny PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7dny RCSB], [https://www.ebi.ac.uk/pdbsum/7dny PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7dny ProSAT]</span></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=7dny FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7dny OCA], [https://pdbe.org/7dny PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7dny RCSB], [https://www.ebi.ac.uk/pdbsum/7dny PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7dny ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Disease == | == Disease == | ||
| - | + | [https://www.uniprot.org/uniprot/ABCB6_HUMAN ABCB6_HUMAN] Ocular coloboma;Dyschromatosis universalis;Colobomatous microphthalmia. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry. ABCB6 mutations are involved in familial pseudohyperkalemia, a dominantly inherited condition characterized by increased serum potassium levels, measured in whole-blood specimens stored at or below room temperature. This condition is not accompanied by clinical symptoms or biological signs except for borderline abnormalities of red cell shape (PubMed:23180570).<ref>PMID:23180570</ref> | |
== Function == | == Function == | ||
| - | + | [https://www.uniprot.org/uniprot/ABCB6_HUMAN ABCB6_HUMAN] Binds heme and porphyrins and functions in their ATP-dependent uptake into the mitochondria. Plays a crucial role in heme synthesis.<ref>PMID:10837493</ref> <ref>PMID:17006453</ref> | |
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
Human ABCB6 is an ATP-binding cassette transporter that regulates heme biosynthesis by translocating various porphyrins from the cytoplasm into the mitochondria. Here we report the cryo-electron microscopy (cryo-EM) structures of human ABCB6 with its substrates, coproporphyrin III (CPIII) and hemin, at 3.5 and 3.7 A resolution, respectively. Metalfree porphyrin CPIII binds to ABCB6 within the central cavity, where its propionic acids form hydrogen bonds with the highly conserved Y550. The resulting structure has an overall fold similar to the inward-facing apo structure, but the two nucleotide-binding domains (NBDs) are slightly closer to each other. In contrast, when ABCB6 binds a metal-centered porphyrin hemin in complex with two glutathione molecules (1 hemin: 2 glutathione), the two NBDs end up much closer together, aligning them to bind and hydrolyze ATP more efficiently. In our structures, a glycine-rich and highly flexible "bulge" loop on TM helix 7 undergoes significant conformational changes associated with substrate binding. Our findings suggest that ABCB6 utilizes at least two distinct mechanisms to fine-tune substrate specificity and transport efficiency. | Human ABCB6 is an ATP-binding cassette transporter that regulates heme biosynthesis by translocating various porphyrins from the cytoplasm into the mitochondria. Here we report the cryo-electron microscopy (cryo-EM) structures of human ABCB6 with its substrates, coproporphyrin III (CPIII) and hemin, at 3.5 and 3.7 A resolution, respectively. Metalfree porphyrin CPIII binds to ABCB6 within the central cavity, where its propionic acids form hydrogen bonds with the highly conserved Y550. The resulting structure has an overall fold similar to the inward-facing apo structure, but the two nucleotide-binding domains (NBDs) are slightly closer to each other. In contrast, when ABCB6 binds a metal-centered porphyrin hemin in complex with two glutathione molecules (1 hemin: 2 glutathione), the two NBDs end up much closer together, aligning them to bind and hydrolyze ATP more efficiently. In our structures, a glycine-rich and highly flexible "bulge" loop on TM helix 7 undergoes significant conformational changes associated with substrate binding. Our findings suggest that ABCB6 utilizes at least two distinct mechanisms to fine-tune substrate specificity and transport efficiency. | ||
| - | Structural Insights into Porphyrin Recognition by the Human ATP-Binding Cassette Transporter ABCB6.,Kim S, Lee SS, Park JG, Kim JW, Ju S, Choi SH, Kim S, Kim NJ, Hong S, Kang JY, Jin MS Mol Cells. 2022 Aug 31;45(8):575-587. doi: 10.14348/molcells.2022.0040. Epub 2022, Jul 28. PMID:35950458<ref>PMID:35950458</ref> | + | Structural Insights into Porphyrin Recognition by the Human ATP-Binding Cassette Transporter ABCB6.,Kim S, Lee SS, Park JG, Kim JW, Ju S, Choi SH, Kim S, Kim NJ, Hong S, Kang JY, Jin MS Mol Cells. 2022 Aug 31;45(8):575-587. doi: 10.14348/molcells.2022.0040. Epub 2022 , Jul 28. PMID:35950458<ref>PMID:35950458</ref> |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
Current revision
Cryo-EM structure of the human ABCB6 (coproporphyrin III-bound)
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Categories: Homo sapiens | Large Structures | Hong S | Jin MS | Kang JY | Kim JW | Kim NJ | Kim S | Lee SS | Park JG
