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6c3p

From Proteopedia

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Current revision

Cryo-EM structure of human KATP bound to ATP and ADP in propeller form

6c3p, resolution 5.60Å

Structural highlights

6c3p is a 8 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Related:	6c3o
Experimental data:	Check to display Experimental Data
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[KCJ11_HUMAN] MODY;Autosomal dominant hyperinsulinism due to Kir6.2 deficiency;Intermediate DEND syndrome;Transient neonatal diabetes mellitus;Permanent neonatal diabetes mellitus;DEND syndrome;Diazoxide-resistant focal hyperinsulinism due to Kir6.2 deficiency;Autosomal recessive hyperinsulinism due to Kir6.2 deficiency. 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. The disease is caused by mutations affecting the gene represented in this entry. Defects in KCNJ11 may contribute to non-insulin-dependent diabetes mellitus (NIDDM), also known as diabetes mellitus type 2. The disease is caused by mutations affecting the gene represented in this entry. [ABCC8_HUMAN] Diazoxide-resistant focal hyperinsulinism due to SUR1 deficiency;Autosomal dominant hyperinsulinism due to SUR1 deficiency;Transient neonatal diabetes mellitus;DEND syndrome;Autosomal recessive hyperinsulinism due to SUR1 deficiency;MODY;Permanent neonatal diabetes mellitus. 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. 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.

Function

[KCJ11_HUMAN] This receptor is controlled by G proteins. Inward rectifier potassium channels are characterized by a greater tendency to allow potassium to flow into the cell rather than out of it. Their voltage dependence is regulated by the concentration of extracellular potassium; as external potassium is raised, the voltage range of the channel opening shifts to more positive voltages. The inward rectification is mainly due to the blockage of outward current by internal magnesium. Can be blocked by extracellular barium (By similarity). Subunit of ATP-sensitive potassium channels (KATP). Can form cardiac and smooth muscle-type KATP channels with ABCC9. KCNJ11 forms the channel pore while ABCC9 is required for activation and regulation.^[1] ^[2] ^[3] [ABCC8_HUMAN] Subunit of the beta-cell ATP-sensitive potassium channel (KATP). Regulator of ATP-sensitive K(+) channels and insulin release.^[4] ^[5]

Publication Abstract from PubMed

In many excitable cells KATP channels respond to intracellular adenosine nucleotides: ATP inhibits while ADP activates. We present two structures of the human pancreatic KATP channel, containing the ABC transporter SUR1 and the inward-rectifier K(+) channel Kir6.2, in the presence of Mg(2+) and nucleotides. These structures, referred to as quatrefoil and propeller forms, were determined by single-particle cryo-EM at 3.9 A and 5.6 A, respectively. In both forms ATP occupies the inhibitory site in Kir6.2. The nucleotide-binding domains of SUR1 are dimerized with Mg(2+)-ATP in the degenerate site and Mg(2+)-ADP in the consensus site. A lasso extension forms an interface between SUR1 and Kir6.2 adjacent to the ATP site in the propeller form, and is disrupted in the quatrefoil form. These structures support the role of SUR1 as an ADP sensor and highlight the lasso extension as a key regulatory element in ADP's ability to override ATP inhibition.

Molecular structure of human KATP in complex with ATP and ADP.,Lee KPK, Chen J, MacKinnon R Elife. 2017 Dec 29;6. doi: 10.7554/eLife.32481. PMID:29286281^[6]

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

References

↑ Tammaro P, Ashcroft FM. A mutation in the ATP-binding site of the Kir6.2 subunit of the KATP channel alters coupling with the SUR2A subunit. J Physiol. 2007 Nov 1;584(Pt 3):743-53. doi: 10.1113/jphysiol.2007.143149. Epub, 2007 Sep 13. PMID:17855752 doi:http://dx.doi.org/10.1113/jphysiol.2007.143149
↑ Cooper PE, McClenaghan C, Chen X, Stary-Weinzinger A, Nichols CG. Conserved functional consequences of disease-associated mutations in the slide helix of Kir6.1 and Kir6.2 subunits of the ATP-sensitive potassium channel. J Biol Chem. 2017 Oct 20;292(42):17387-17398. doi: 10.1074/jbc.M117.804971. Epub , 2017 Aug 23. PMID:28842488 doi:http://dx.doi.org/10.1074/jbc.M117.804971
↑ Babenko AP, Gonzalez G, Aguilar-Bryan L, Bryan J. Reconstituted human cardiac KATP channels: functional identity with the native channels from the sarcolemma of human ventricular cells. Circ Res. 1998 Nov 30;83(11):1132-43. PMID:9831708
↑ Saint-Martin C, Zhou Q, Martin GM, Vaury C, Leroy G, Arnoux JB, de Lonlay P, Shyng SL, Bellanne-Chantelot C. Monoallelic ABCC8 mutations are a common cause of diazoxide-unresponsive diffuse form of congenital hyperinsulinism. Clin Genet. 2015 May;87(5):448-54. doi: 10.1111/cge.12428. Epub 2014 Jun 6. PMID:24814349 doi:http://dx.doi.org/10.1111/cge.12428
↑ Harel S, Cohen AS, Hussain K, Flanagan SE, Schlade-Bartusiak K, Patel M, Courtade J, Li JB, Van Karnebeek C, Kurata H, Ellard S, Chanoine JP, Gibson WT. Alternating hypoglycemia and hyperglycemia in a toddler with a homozygous p.R1419H ABCC8 mutation: an unusual clinical picture. J Pediatr Endocrinol Metab. 2015 Mar;28(3-4):345-51. doi: 10.1515/jpem-2014-0265. PMID:25720052 doi:http://dx.doi.org/10.1515/jpem-2014-0265
↑ Lee KPK, Chen J, MacKinnon R. Molecular structure of human KATP in complex with ATP and ADP. Elife. 2017 Dec 29;6. doi: 10.7554/eLife.32481. PMID:29286281 doi:http://dx.doi.org/10.7554/eLife.32481

1 Structural highlights
2 Disease
3 Function
4 Publication Abstract from PubMed
5 See Also
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/6c3p"

@@ Line 3: / Line 3: @@
 <SX load='6c3p' size='340' side='right' viewer='molstar' caption='[[6c3p]], [[Resolution|resolution]] 5.60&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6c3p]] is a 8 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6C3P OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6C3P FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6c3p]] is a 8 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6C3P OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6C3P FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ADP:ADENOSINE-5-DIPHOSPHATE'>ADP</scene>, <scene name='pdbligand=ATP:ADENOSINE-5-TRIPHOSPHATE'>ATP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ADP:ADENOSINE-5-DIPHOSPHATE'>ADP</scene>, <scene name='pdbligand=ATP:ADENOSINE-5-TRIPHOSPHATE'>ATP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[6c3o|6c3o]]</td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6c3p FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6c3p OCA], [http://pdbe.org/6c3p PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6c3p RCSB], [http://www.ebi.ac.uk/pdbsum/6c3p PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6c3p ProSAT]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6c3p FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6c3p OCA], [http://pdbe.org/6c3p PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6c3p RCSB], [http://www.ebi.ac.uk/pdbsum/6c3p PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6c3p ProSAT]</span></td></tr>
 </table>
 == Disease ==

6c3p

From Proteopedia

Current revision

Cryo-EM structure of human KATP bound to ATP and ADP in propeller form

Structural highlights

Disease

Function

Publication Abstract from PubMed

See Also

References

Contents

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