|
|
| Line 1: |
Line 1: |
| | | | |
| | ==Structure of the human SLO3 gating ring== | | ==Structure of the human SLO3 gating ring== |
| - | <StructureSection load='4hpf' size='340' side='right' caption='[[4hpf]], [[Resolution|resolution]] 3.40Å' scene=''> | + | <StructureSection load='4hpf' size='340' side='right'caption='[[4hpf]], [[Resolution|resolution]] 3.40Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4hpf]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4HPF OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4HPF FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4hpf]] 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=4HPF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4HPF FirstGlance]. <br> |
| - | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">KCNMA3, KCNMC1, KCNU1, SLO3 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | + | </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=4hpf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4hpf OCA], [https://pdbe.org/4hpf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4hpf RCSB], [https://www.ebi.ac.uk/pdbsum/4hpf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4hpf ProSAT]</span></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=4hpf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4hpf OCA], [http://pdbe.org/4hpf PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4hpf RCSB], [http://www.ebi.ac.uk/pdbsum/4hpf PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4hpf ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/KCNU1_HUMAN KCNU1_HUMAN]] Testis-specific potassium channel activated by both intracellular pH and membrane voltage that mediates export of K(+). May represent the primary spermatozoan K(+) current. In contrast to KCNMA1/SLO1, it is not activated by Ca(2+) or Mg(2+). Critical for fertility. May play an important role in sperm osmoregulation required for the acquisition of normal morphology and motility when faced with osmotic challenges, such as those experienced after mixing with seminal fluid and entry into the vagina.<ref>PMID:23129643</ref> | + | [https://www.uniprot.org/uniprot/KCNU1_HUMAN KCNU1_HUMAN] Testis-specific potassium channel activated by both intracellular pH and membrane voltage that mediates export of K(+). May represent the primary spermatozoan K(+) current. In contrast to KCNMA1/SLO1, it is not activated by Ca(2+) or Mg(2+). Critical for fertility. May play an important role in sperm osmoregulation required for the acquisition of normal morphology and motility when faced with osmotic challenges, such as those experienced after mixing with seminal fluid and entry into the vagina.<ref>PMID:23129643</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
| Line 18: |
Line 17: |
| | </div> | | </div> |
| | <div class="pdbe-citations 4hpf" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 4hpf" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Potassium channel 3D structures|Potassium channel 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Leonetti, M D]] | + | [[Category: Large Structures]] |
| - | [[Category: MacKinnon, R]] | + | [[Category: Leonetti MD]] |
| - | [[Category: Yuan, P]] | + | [[Category: MacKinnon R]] |
| - | [[Category: Membrane protein]] | + | [[Category: Yuan P]] |
| - | [[Category: Ph-gated]]
| + | |
| - | [[Category: Potassium channel]]
| + | |
| - | [[Category: Transport protein]]
| + | |
| Structural highlights
Function
KCNU1_HUMAN Testis-specific potassium channel activated by both intracellular pH and membrane voltage that mediates export of K(+). May represent the primary spermatozoan K(+) current. In contrast to KCNMA1/SLO1, it is not activated by Ca(2+) or Mg(2+). Critical for fertility. May play an important role in sperm osmoregulation required for the acquisition of normal morphology and motility when faced with osmotic challenges, such as those experienced after mixing with seminal fluid and entry into the vagina.[1]
Publication Abstract from PubMed
The activation of eukaryotic SLO K(+) channels by intracellular cues, mediated by a cytoplasmic structure called the gating ring, is central to their physiological roles. SLO3 channels are exclusively expressed in mammalian sperm, where variations of intracellular pH are critical to cellular function. Previous studies primarily focused on the mouse SLO3 orthologue and revealed that, in murine sperm, SLO3 mediates a voltage- and alkalization-activated K(+) current essential to male fertility. Here we investigate the activation of the human SLO3 channel by intracellular pH at the functional and structural level. By using electrophysiology in a heterologous system, we show that human SLO3 opens upon intracellular pH increase and that its expression and functional properties are modulated by LRRC52, a testis-specific accessory subunit. We next present the crystal structure of the human SLO3 gating ring. Comparison with the known structures of the corresponding domain from SLO1, a Ca(2+)-activated homologue, suggests that the SLO3 gating ring structure may represent an open state. Together, these results present insights into the function of a protein expected to be critical for human reproduction and provide a framework to study the mechanism of pH gating in SLO3 channels.
Functional and structural analysis of the human SLO3 pH- and voltage-gated K+ channel.,Leonetti MD, Yuan P, Hsiung Y, Mackinnon R Proc Natl Acad Sci U S A. 2012 Nov 20;109(47):19274-9. doi:, 10.1073/pnas.1215078109. Epub 2012 Nov 5. PMID:23129643[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Leonetti MD, Yuan P, Hsiung Y, Mackinnon R. Functional and structural analysis of the human SLO3 pH- and voltage-gated K+ channel. Proc Natl Acad Sci U S A. 2012 Nov 20;109(47):19274-9. doi:, 10.1073/pnas.1215078109. Epub 2012 Nov 5. PMID:23129643 doi:http://dx.doi.org/10.1073/pnas.1215078109
- ↑ Leonetti MD, Yuan P, Hsiung Y, Mackinnon R. Functional and structural analysis of the human SLO3 pH- and voltage-gated K+ channel. Proc Natl Acad Sci U S A. 2012 Nov 20;109(47):19274-9. doi:, 10.1073/pnas.1215078109. Epub 2012 Nov 5. PMID:23129643 doi:http://dx.doi.org/10.1073/pnas.1215078109
|
