6v35

From Proteopedia

(Difference between revisions)

Revision as of 09:23, 25 December 2019

Cryo-EM structure of Ca2+-free hsSlo1-beta4 channel complex

Structural highlights

6v35 is a 8 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, ,
Related:	6v22
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[KCMB4_HUMAN] Regulatory subunit of the calcium activated potassium KCNMA1 (maxiK) channel. Modulates the calcium sensitivity and gating kinetics of KCNMA1, thereby contributing to KCNMA1 channel diversity. Decreases the gating kinetics and calcium sensitivity of the KCNMA1 channel, but with fast deactivation kinetics. May decrease KCNMA1 channel openings at low calcium concentrations but increases channel openings at high calcium concentrations. Makes KCNMA1 channel resistant to 100 nM charybdotoxin (CTX) toxin concentrations.^[1] ^[2] ^[3]

Publication Abstract from PubMed

Slo1 is a Ca(2+)- and voltage-activated K(+) channel that underlies skeletal and smooth muscle contraction, audition, hormone secretion and neurotransmitter release. In mammals, Slo1 is regulated by auxiliary proteins that confer tissue-specific gating and pharmacological properties. This study presents cryo-EM structures of Slo1 in complex with the auxiliary protein, beta4. Four beta4, each containing two transmembrane helices, encircle Slo1, contacting it through helical interactions inside the membrane. On the extracellular side, b4 forms a tetrameric crown over the pore. Structures with high and low Ca(2+) concentrations show that identical gating conformations occur in the absence and presence of beta4, implying that beta4 serves to modulate the relative stabilities of 'pre-existing' conformations rather than creating new ones. The effects of beta4 on scorpion toxin inhibition kinetics are explained by the crown, which constrains access but does not prevent binding.

Molecular structures of the human Slo1 K(+) channel in complex with beta4.,Tao X, MacKinnon R Elife. 2019 Dec 9;8. pii: 51409. doi: 10.7554/eLife.51409. PMID:31815672^[4]

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

References

↑ Brenner R, Jegla TJ, Wickenden A, Liu Y, Aldrich RW. Cloning and functional characterization of novel large conductance calcium-activated potassium channel beta subunits, hKCNMB3 and hKCNMB4. J Biol Chem. 2000 Mar 3;275(9):6453-61. PMID:10692449
↑ Meera P, Wallner M, Toro L. A neuronal beta subunit (KCNMB4) makes the large conductance, voltage- and Ca2+-activated K+ channel resistant to charybdotoxin and iberiotoxin. Proc Natl Acad Sci U S A. 2000 May 9;97(10):5562-7. PMID:10792058 doi:http://dx.doi.org/10.1073/pnas.100118597
↑ Behrens R, Nolting A, Reimann F, Schwarz M, Waldschutz R, Pongs O. hKCNMB3 and hKCNMB4, cloning and characterization of two members of the large-conductance calcium-activated potassium channel beta subunit family. FEBS Lett. 2000 May 26;474(1):99-106. PMID:10828459
↑ Tao X, MacKinnon R. Molecular structures of the human Slo1 K(+) channel in complex with beta4. Elife. 2019 Dec 9;8. pii: 51409. doi: 10.7554/eLife.51409. PMID:31815672 doi:http://dx.doi.org/10.7554/eLife.51409

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/6v35"

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 6v35 is ON HOLD
+==Cryo-EM structure of Ca2+-free hsSlo1-beta4 channel complex==
+<StructureSection load='6v35' size='340' side='right'caption='[[6v35]], [[Resolution|resolution]] 3.50&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[6v35]] is a 8 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6V35 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6V35 FirstGlance]. <br>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CLR:CHOLESTEROL'>CLR</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=PGW:(1R)-2-{[(S)-{[(2S)-2,3-DIHYDROXYPROPYL]OXY}(HYDROXY)PHOSPHORYL]OXY}-1-[(HEXADECANOYLOXY)METHYL]ETHYL+(9Z)-OCTADEC-9-ENOATE'>PGW</scene></td></tr>
+<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[6v22|6v22]]</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=6v35 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6v35 OCA], [http://pdbe.org/6v35 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6v35 RCSB], [http://www.ebi.ac.uk/pdbsum/6v35 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6v35 ProSAT]</span></td></tr>
+</table>
+== Function ==
+[[http://www.uniprot.org/uniprot/KCMB4_HUMAN KCMB4_HUMAN]] Regulatory subunit of the calcium activated potassium KCNMA1 (maxiK) channel. Modulates the calcium sensitivity and gating kinetics of KCNMA1, thereby contributing to KCNMA1 channel diversity. Decreases the gating kinetics and calcium sensitivity of the KCNMA1 channel, but with fast deactivation kinetics. May decrease KCNMA1 channel openings at low calcium concentrations but increases channel openings at high calcium concentrations. Makes KCNMA1 channel resistant to 100 nM charybdotoxin (CTX) toxin concentrations.<ref>PMID:10692449</ref> <ref>PMID:10792058</ref> <ref>PMID:10828459</ref>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Slo1 is a Ca(2+)- and voltage-activated K(+) channel that underlies skeletal and smooth muscle contraction, audition, hormone secretion and neurotransmitter release. In mammals, Slo1 is regulated by auxiliary proteins that confer tissue-specific gating and pharmacological properties. This study presents cryo-EM structures of Slo1 in complex with the auxiliary protein, beta4. Four beta4, each containing two transmembrane helices, encircle Slo1, contacting it through helical interactions inside the membrane. On the extracellular side, b4 forms a tetrameric crown over the pore. Structures with high and low Ca(2+) concentrations show that identical gating conformations occur in the absence and presence of beta4, implying that beta4 serves to modulate the relative stabilities of 'pre-existing' conformations rather than creating new ones. The effects of beta4 on scorpion toxin inhibition kinetics are explained by the crown, which constrains access but does not prevent binding.
-Authors:
+Molecular structures of the human Slo1 K(+) channel in complex with beta4.,Tao X, MacKinnon R Elife. 2019 Dec 9;8. pii: 51409. doi: 10.7554/eLife.51409. PMID:31815672<ref>PMID:31815672</ref>
-Description:
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
+<div class="pdbe-citations 6v35" style="background-color:#fffaf0;"></div>
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Large Structures]]
+[[Category: MacKinnon, R]]
+[[Category: Tao, X]]
+[[Category: Beta4 subunit]]
+[[Category: Bk channel]]
+[[Category: High conductance ca2+-activated k+ channel]]
+[[Category: Maxik channel]]
+[[Category: Slo1 beta subunit]]
+[[Category: Slo1 channel]]
+[[Category: Transport protein]]

6v35

From Proteopedia

Revision as of 09:23, 25 December 2019

Cryo-EM structure of Ca2+-free hsSlo1-beta4 channel complex

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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