7xum: Difference between revisions
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== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[7xum]] 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=7XUM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7XUM FirstGlance]. <br> | <table><tr><td colspan='2'>[[7xum]] 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=7XUM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7XUM FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CU:COPPER+(II)+ION'>CU</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]] 3.8Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CU:COPPER+(II)+ION'>CU</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=7xum FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7xum OCA], [https://pdbe.org/7xum PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7xum RCSB], [https://www.ebi.ac.uk/pdbsum/7xum PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7xum 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=7xum FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7xum OCA], [https://pdbe.org/7xum PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7xum RCSB], [https://www.ebi.ac.uk/pdbsum/7xum PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7xum ProSAT]</span></td></tr> | ||
</table> | </table> | ||
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The P-type ATPase ATP7B exports cytosolic copper and plays an essential role in the regulation of cellular copper homeostasis. Mutants of ATP7B cause Wilson disease (WD), an autosomal recessive disorder of copper metabolism. Here, we present cryoelectron microscopy (cryo-EM) structures of human ATP7B in the E1 state in the apo, the putative copper-bound, and the putative cisplatin-bound forms. In ATP7B, the N-terminal sixth metal-binding domain (MBD6) binds at the cytosolic copper entry site of the transmembrane domain (TMD), facilitating the delivery of copper from the MBD6 to the TMD. The sulfur-containing residues in the TMD of ATP7B mark the copper transport pathway. By comparing structures of the E1 state human ATP7B and E2-P(i) state frog ATP7B, we propose the ATP-driving copper transport model of ATP7B. These structures not only advance our understanding of the mechanisms of ATP7B-mediated copper export but can also guide the development of therapeutics for the treatment of WD. | The P-type ATPase ATP7B exports cytosolic copper and plays an essential role in the regulation of cellular copper homeostasis. Mutants of ATP7B cause Wilson disease (WD), an autosomal recessive disorder of copper metabolism. Here, we present cryoelectron microscopy (cryo-EM) structures of human ATP7B in the E1 state in the apo, the putative copper-bound, and the putative cisplatin-bound forms. In ATP7B, the N-terminal sixth metal-binding domain (MBD6) binds at the cytosolic copper entry site of the transmembrane domain (TMD), facilitating the delivery of copper from the MBD6 to the TMD. The sulfur-containing residues in the TMD of ATP7B mark the copper transport pathway. By comparing structures of the E1 state human ATP7B and E2-P(i) state frog ATP7B, we propose the ATP-driving copper transport model of ATP7B. These structures not only advance our understanding of the mechanisms of ATP7B-mediated copper export but can also guide the development of therapeutics for the treatment of WD. | ||
Structures of the human Wilson disease copper transporter ATP7B.,Yang GM, Xu L, Wang RM, Tao X, Zheng ZW, Chang S, Ma D, Zhao C, Dong Y, Wu S, Guo J, Wu ZY Cell Rep. 2023 | Structures of the human Wilson disease copper transporter ATP7B.,Yang GM, Xu L, Wang RM, Tao X, Zheng ZW, Chang S, Ma D, Zhao C, Dong Y, Wu S, Guo J, Wu ZY Cell Rep. 2023 May 30;42(5):112417. doi: 10.1016/j.celrep.2023.112417. Epub 2023 , Apr 18. PMID:37074913<ref>PMID:37074913</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> | ||