6coy: Difference between revisions

Revision as of 07:38, 14 June 2018

Human CLC-1 chloride ion channel, transmembrane domain

Structural highlights

6coy is a 2 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	CL
Related:	6coz
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[CLCN1_HUMAN] Thomsen and Becker disease. 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

[CLCN1_HUMAN] Voltage-gated chloride channel. Chloride channels have several functions including the regulation of cell volume; membrane potential stabilization, signal transduction and transepithelial transport.^[1] ^[2] ^[3] ^[4] ^[5] ^[6] ^[7] ^[8] ^[9]

Publication Abstract from PubMed

CLC channels mediate passive Cl(-) conduction, while CLC transporters mediate active Cl(-) transport coupled to H(+) transport in the opposite direction. The distinction between CLC-0/1/2 channels and CLC transporters seems undetectable by amino acid sequence. To understand why they are different functionally we determined the structure of the human CLC-1 channel. Its 'glutamate gate' residue, known to mediate proton transfer in CLC transporters, adopts a location in the structure that appears to preclude it from its transport function. Furthermore, smaller side chains produce a wider pore near the intracellular surface, potentially reducing a kinetic barrier for Cl(-) conduction. When the corresponding residues are mutated in a transporter, it is converted to a channel. Finally, Cl(-) at key sites in the pore appear to interact with reduced affinity compared to transporters. Thus, subtle differences in glutamate gate conformation, internal pore diameter and Cl(-) affinity distinguish CLC channels and transporters.

Structure of the CLC-1 chloride channel from Homo sapiens.,Park E, MacKinnon R Elife. 2018 May 29;7. pii: 36629. doi: 10.7554/eLife.36629. PMID:29809153^[10]

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

References

↑ Ryan A, Rudel R, Kuchenbecker M, Fahlke C. A novel alteration of muscle chloride channel gating in myotonia levior. J Physiol. 2002 Dec 1;545(Pt 2):345-54. PMID:12456816
↑ Ulzi G, Lecchi M, Sansone V, Redaelli E, Corti E, Saccomanno D, Pagliarani S, Corti S, Magri F, Raimondi M, D'Angelo G, Modoni A, Bresolin N, Meola G, Wanke E, Comi GP, Lucchiari S. Myotonia congenita: novel mutations in CLCN1 gene and functional characterizations in Italian patients. J Neurol Sci. 2012 Jul 15;318(1-2):65-71. doi: 10.1016/j.jns.2012.03.024. Epub, 2012 Apr 21. PMID:22521272 doi:https://dx.doi.org/10.1016/j.jns.2012.03.024
↑ Portaro S, Altamura C, Licata N, Camerino GM, Imbrici P, Musumeci O, Rodolico C, Conte Camerino D, Toscano A, Desaphy JF. Clinical, Molecular, and Functional Characterization of CLCN1 Mutations in Three Families with Recessive Myotonia Congenita. Neuromolecular Med. 2015 Sep;17(3):285-96. doi: 10.1007/s12017-015-8356-8. Epub, 2015 May 26. PMID:26007199 doi:https://dx.doi.org/10.1007/s12017-015-8356-8
↑ Ronstedt K, Sternberg D, Detro-Dassen S, Gramkow T, Begemann B, Becher T, Kilian P, Grieschat M, Machtens JP, Schmalzing G, Fischer M, Fahlke C. Impaired surface membrane insertion of homo- and heterodimeric human muscle chloride channels carrying amino-terminal myotonia-causing mutations. Sci Rep. 2015 Oct 27;5:15382. doi: 10.1038/srep15382. PMID:26502825 doi:https://dx.doi.org/10.1038/srep15382
↑ Vindas-Smith R, Fiore M, Vasquez M, Cuenca P, Del Valle G, Lagostena L, Gaitan-Penas H, Estevez R, Pusch M, Morales F. Identification and Functional Characterization of CLCN1 Mutations Found in Nondystrophic Myotonia Patients. Hum Mutat. 2016 Jan;37(1):74-83. doi: 10.1002/humu.22916. Epub 2015 Oct 28. PMID:26510092 doi:https://dx.doi.org/10.1002/humu.22916
↑ Lorenz C, Meyer-Kleine C, Steinmeyer K, Koch MC, Jentsch TJ. Genomic organization of the human muscle chloride channel CIC-1 and analysis of novel mutations leading to Becker-type myotonia. Hum Mol Genet. 1994 Jun;3(6):941-6. PMID:7951242
↑ Steinmeyer K, Lorenz C, Pusch M, Koch MC, Jentsch TJ. Multimeric structure of ClC-1 chloride channel revealed by mutations in dominant myotonia congenita (Thomsen). EMBO J. 1994 Feb 15;13(4):737-43. PMID:8112288
↑ Fahlke C, Beck CL, George AL Jr. A mutation in autosomal dominant myotonia congenita affects pore properties of the muscle chloride channel. Proc Natl Acad Sci U S A. 1997 Mar 18;94(6):2729-34. PMID:9122265
↑ Kubisch C, Schmidt-Rose T, Fontaine B, Bretag AH, Jentsch TJ. ClC-1 chloride channel mutations in myotonia congenita: variable penetrance of mutations shifting the voltage dependence. Hum Mol Genet. 1998 Oct;7(11):1753-60. PMID:9736777
↑ Park E, MacKinnon R. Structure of the CLC-1 chloride channel from Homo sapiens. Elife. 2018 May 29;7. pii: 36629. doi: 10.7554/eLife.36629. PMID:29809153 doi:https://dx.doi.org/10.7554/eLife.36629

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OCA

[1] Ryan A, Rudel R, Kuchenbecker M, Fahlke C. A novel alteration of muscle chloride channel gating in myotonia levior. J Physiol. 2002 Dec 1;545(Pt 2):345-54. PMID:12456816

[2] Ulzi G, Lecchi M, Sansone V, Redaelli E, Corti E, Saccomanno D, Pagliarani S, Corti S, Magri F, Raimondi M, D'Angelo G, Modoni A, Bresolin N, Meola G, Wanke E, Comi GP, Lucchiari S. Myotonia congenita: novel mutations in CLCN1 gene and functional characterizations in Italian patients. J Neurol Sci. 2012 Jul 15;318(1-2):65-71. doi: 10.1016/j.jns.2012.03.024. Epub, 2012 Apr 21. PMID:22521272 doi:https://dx.doi.org/10.1016/j.jns.2012.03.024

[3] Portaro S, Altamura C, Licata N, Camerino GM, Imbrici P, Musumeci O, Rodolico C, Conte Camerino D, Toscano A, Desaphy JF. Clinical, Molecular, and Functional Characterization of CLCN1 Mutations in Three Families with Recessive Myotonia Congenita. Neuromolecular Med. 2015 Sep;17(3):285-96. doi: 10.1007/s12017-015-8356-8. Epub, 2015 May 26. PMID:26007199 doi:https://dx.doi.org/10.1007/s12017-015-8356-8

[4] Ronstedt K, Sternberg D, Detro-Dassen S, Gramkow T, Begemann B, Becher T, Kilian P, Grieschat M, Machtens JP, Schmalzing G, Fischer M, Fahlke C. Impaired surface membrane insertion of homo- and heterodimeric human muscle chloride channels carrying amino-terminal myotonia-causing mutations. Sci Rep. 2015 Oct 27;5:15382. doi: 10.1038/srep15382. PMID:26502825 doi:https://dx.doi.org/10.1038/srep15382

[5] Vindas-Smith R, Fiore M, Vasquez M, Cuenca P, Del Valle G, Lagostena L, Gaitan-Penas H, Estevez R, Pusch M, Morales F. Identification and Functional Characterization of CLCN1 Mutations Found in Nondystrophic Myotonia Patients. Hum Mutat. 2016 Jan;37(1):74-83. doi: 10.1002/humu.22916. Epub 2015 Oct 28. PMID:26510092 doi:https://dx.doi.org/10.1002/humu.22916

[6] Lorenz C, Meyer-Kleine C, Steinmeyer K, Koch MC, Jentsch TJ. Genomic organization of the human muscle chloride channel CIC-1 and analysis of novel mutations leading to Becker-type myotonia. Hum Mol Genet. 1994 Jun;3(6):941-6. PMID:7951242

[7] Steinmeyer K, Lorenz C, Pusch M, Koch MC, Jentsch TJ. Multimeric structure of ClC-1 chloride channel revealed by mutations in dominant myotonia congenita (Thomsen). EMBO J. 1994 Feb 15;13(4):737-43. PMID:8112288

[8] Fahlke C, Beck CL, George AL Jr. A mutation in autosomal dominant myotonia congenita affects pore properties of the muscle chloride channel. Proc Natl Acad Sci U S A. 1997 Mar 18;94(6):2729-34. PMID:9122265

[9] Kubisch C, Schmidt-Rose T, Fontaine B, Bretag AH, Jentsch TJ. ClC-1 chloride channel mutations in myotonia congenita: variable penetrance of mutations shifting the voltage dependence. Hum Mol Genet. 1998 Oct;7(11):1753-60. PMID:9736777

[10] Park E, MacKinnon R. Structure of the CLC-1 chloride channel from Homo sapiens. Elife. 2018 May 29;7. pii: 36629. doi: 10.7554/eLife.36629. PMID:29809153 doi:https://dx.doi.org/10.7554/eLife.36629

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@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 6coy is ON HOLD  until Paper Publication
+==Human CLC-1 chloride ion channel, transmembrane domain==
+<StructureSection load='6coy' size='340' side='right' caption='[[6coy]], [[Resolution|resolution]] 3.36&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[6coy]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6COY OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6COY FirstGlance]. <br>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene></td></tr>
+<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[6coz|6coz]]</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=6coy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6coy OCA], [http://pdbe.org/6coy PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6coy RCSB], [http://www.ebi.ac.uk/pdbsum/6coy PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6coy ProSAT]</span></td></tr>
+</table>
+== Disease ==
+[[http://www.uniprot.org/uniprot/CLCN1_HUMAN CLCN1_HUMAN]] Thomsen and Becker disease. 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 ==
+[[http://www.uniprot.org/uniprot/CLCN1_HUMAN CLCN1_HUMAN]] Voltage-gated chloride channel. Chloride channels have several functions including the regulation of cell volume; membrane potential stabilization, signal transduction and transepithelial transport.<ref>PMID:12456816</ref> <ref>PMID:22521272</ref> <ref>PMID:26007199</ref> <ref>PMID:26502825</ref> <ref>PMID:26510092</ref> <ref>PMID:7951242</ref> <ref>PMID:8112288</ref> <ref>PMID:9122265</ref> <ref>PMID:9736777</ref>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+CLC channels mediate passive Cl(-) conduction, while CLC transporters mediate active Cl(-) transport coupled to H(+) transport in the opposite direction. The distinction between CLC-0/1/2 channels and CLC transporters seems undetectable by amino acid sequence. To understand why they are different functionally we determined the structure of the human CLC-1 channel. Its 'glutamate gate' residue, known to mediate proton transfer in CLC transporters, adopts a location in the structure that appears to preclude it from its transport function. Furthermore, smaller side chains produce a wider pore near the intracellular surface, potentially reducing a kinetic barrier for Cl(-) conduction. When the corresponding residues are mutated in a transporter, it is converted to a channel. Finally, Cl(-) at key sites in the pore appear to interact with reduced affinity compared to transporters. Thus, subtle differences in glutamate gate conformation, internal pore diameter and Cl(-) affinity distinguish CLC channels and transporters.
-Authors:
+Structure of the CLC-1 chloride channel from Homo sapiens.,Park E, MacKinnon R Elife. 2018 May 29;7. pii: 36629. doi: 10.7554/eLife.36629. PMID:29809153<ref>PMID:29809153</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 6coy" style="background-color:#fffaf0;"></div>
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: MacKinnon, R]]
+[[Category: Park, E]]
+[[Category: Channel]]
+[[Category: Chloride]]
+[[Category: Clc]]
+[[Category: Transport protein]]

6coy: Difference between revisions

Revision as of 07:38, 14 June 2018

Human CLC-1 chloride ion channel, transmembrane domain

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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