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==Structure of human prestin in the presence of NaCl== | ==Structure of human prestin in the presence of NaCl== | ||
<StructureSection load='7lgu' size='340' side='right'caption='[[7lgu]]' scene=''> | <StructureSection load='7lgu' size='340' side='right'caption='[[7lgu]], [[Resolution|resolution]] 2.30Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7LGU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7LGU FirstGlance]. <br> | <table><tr><td colspan='2'>[[7lgu]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7LGU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7LGU FirstGlance]. <br> | ||
</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=7lgu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7lgu OCA], [https://pdbe.org/7lgu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7lgu RCSB], [https://www.ebi.ac.uk/pdbsum/7lgu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7lgu ProSAT]</span></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=C14:TETRADECANE'>C14</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=CLR:CHOLESTEROL'>CLR</scene>, <scene name='pdbligand=D10:DECANE'>D10</scene>, <scene name='pdbligand=D12:DODECANE'>D12</scene>, <scene name='pdbligand=HEX:HEXANE'>HEX</scene>, <scene name='pdbligand=HP6:HEPTANE'>HP6</scene>, <scene name='pdbligand=OCT:N-OCTANE'>OCT</scene></td></tr> | ||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">SLC26A5, PRES ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=7lgu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7lgu OCA], [https://pdbe.org/7lgu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7lgu RCSB], [https://www.ebi.ac.uk/pdbsum/7lgu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7lgu ProSAT]</span></td></tr> | |||
</table> | </table> | ||
== Disease == | |||
[[https://www.uniprot.org/uniprot/S26A5_HUMAN S26A5_HUMAN]] Autosomal recessive non-syndromic sensorineural deafness type DFNB. The disease is caused by variants affecting the gene represented in this entry. | |||
== Function == | |||
[[https://www.uniprot.org/uniprot/S26A5_HUMAN S26A5_HUMAN]] Motor protein that converts auditory stimuli to length changes in outer hair cells and mediates sound amplification in the mammalian hearing organ. Prestin is a bidirectional voltage-to-force converter, it can operate at microsecond rates. It uses cytoplasmic anions as extrinsic voltage sensors, probably chloride and bicarbonate. After binding to a site with millimolar affinity, these anions are translocated across the membrane in response to changes in the transmembrane voltage. They move towards the extracellular surface following hyperpolarization, and towards the cytoplasmic side in response to depolarization. As a consequence, this translocation triggers conformational changes in the protein that ultimately alter its surface area in the plane of the plasma membrane. The area decreases when the anion is near the cytoplasmic face of the membrane (short state), and increases when the ion has crossed the membrane to the outer surface (long state). So, it acts as an incomplete transporter. It swings anions across the membrane, but does not allow these anions to dissociate and escape to the extracellular space. Salicylate, an inhibitor of outer hair cell motility, acts as competitive antagonist at the prestin anion-binding site (By similarity). | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Hearing involves two fundamental processes: mechano-electrical transduction and signal amplification. Despite decades of studies, the molecular bases for both remain elusive. Here, we show how prestin, the electromotive molecule of outer hair cells (OHCs) that senses both voltage and membrane tension, mediates signal amplification by coupling conformational changes to alterations in membrane surface area. Cryoelectron microscopy (cryo-EM) structures of human prestin bound with chloride or salicylate at a common "anion site" adopt contracted or expanded states, respectively. Prestin is ensconced within a perimeter of well-ordered lipids, through which it induces dramatic deformation in the membrane and couples protein conformational changes to the bulk membrane. Together with computational studies, we illustrate how the anion site is allosterically coupled to changes in the transmembrane domain cross-sectional area and the surrounding membrane. These studies provide insight into OHC electromotility by providing a structure-based mechanism of the membrane motor prestin. | |||
Molecular mechanism of prestin electromotive signal amplification.,Ge J, Elferich J, Dehghani-Ghahnaviyeh S, Zhao Z, Meadows M, von Gersdorff H, Tajkhorshid E, Gouaux E Cell. 2021 Aug 10. pii: S0092-8674(21)00893-X. doi: 10.1016/j.cell.2021.07.034. PMID:34390643<ref>PMID:34390643</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 7lgu" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Human]] | |||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Ge J]] | [[Category: Ge, J]] | ||
[[Category: Gouaux E]] | [[Category: Gouaux, E]] | ||
[[Category: Lipid interaction]] | |||
[[Category: Membrane protein]] | |||
[[Category: Transporter family]] | |||
Revision as of 12:37, 15 September 2021
Structure of human prestin in the presence of NaClStructure of human prestin in the presence of NaCl
Structural highlights
Disease[S26A5_HUMAN] Autosomal recessive non-syndromic sensorineural deafness type DFNB. The disease is caused by variants affecting the gene represented in this entry. Function[S26A5_HUMAN] Motor protein that converts auditory stimuli to length changes in outer hair cells and mediates sound amplification in the mammalian hearing organ. Prestin is a bidirectional voltage-to-force converter, it can operate at microsecond rates. It uses cytoplasmic anions as extrinsic voltage sensors, probably chloride and bicarbonate. After binding to a site with millimolar affinity, these anions are translocated across the membrane in response to changes in the transmembrane voltage. They move towards the extracellular surface following hyperpolarization, and towards the cytoplasmic side in response to depolarization. As a consequence, this translocation triggers conformational changes in the protein that ultimately alter its surface area in the plane of the plasma membrane. The area decreases when the anion is near the cytoplasmic face of the membrane (short state), and increases when the ion has crossed the membrane to the outer surface (long state). So, it acts as an incomplete transporter. It swings anions across the membrane, but does not allow these anions to dissociate and escape to the extracellular space. Salicylate, an inhibitor of outer hair cell motility, acts as competitive antagonist at the prestin anion-binding site (By similarity). Publication Abstract from PubMedHearing involves two fundamental processes: mechano-electrical transduction and signal amplification. Despite decades of studies, the molecular bases for both remain elusive. Here, we show how prestin, the electromotive molecule of outer hair cells (OHCs) that senses both voltage and membrane tension, mediates signal amplification by coupling conformational changes to alterations in membrane surface area. Cryoelectron microscopy (cryo-EM) structures of human prestin bound with chloride or salicylate at a common "anion site" adopt contracted or expanded states, respectively. Prestin is ensconced within a perimeter of well-ordered lipids, through which it induces dramatic deformation in the membrane and couples protein conformational changes to the bulk membrane. Together with computational studies, we illustrate how the anion site is allosterically coupled to changes in the transmembrane domain cross-sectional area and the surrounding membrane. These studies provide insight into OHC electromotility by providing a structure-based mechanism of the membrane motor prestin. Molecular mechanism of prestin electromotive signal amplification.,Ge J, Elferich J, Dehghani-Ghahnaviyeh S, Zhao Z, Meadows M, von Gersdorff H, Tajkhorshid E, Gouaux E Cell. 2021 Aug 10. pii: S0092-8674(21)00893-X. doi: 10.1016/j.cell.2021.07.034. PMID:34390643[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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