Sandbox Reserved 1653: Difference between revisions

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1: IH, 2:OH]]
1: IH, 2:OH]]
Piezo1 possesses delicate force sensing and mechanotransduction mechanisms. Here, we explain how Piezo1 channels sense and transduce mechanical force
Piezo1 possesses delicate force sensing and mechanotransduction mechanisms. Here, we explain how Piezo1 channels sense and transduce mechanical forces to gate the central ion-conducting pore.
to gate the central ion-conducting pore.
Piezo1 can sense membrane tension through changes in the local curvature of the membrane and the channel opens in response to this change thanks to this structure.<ref name ="Piezo Senses Tension"/>
Piezo1 can sense membrane tension through changes in the local curvature of the membrane and channel open in response to this change thanks to this structure.<ref name ="Piezo Senses Tension"/>
Indeed, mPiezo trimer is a non-planar conformation inside lipid bilayer, it produces a local dome-shaped deformation of the membrane. In cells, this membrane curvature project towards the cytoplasm and some electrostatic interactions stabilize the trimeric assembly in its curved conformation.<ref name = "nv article"> DOI 10.7554/eLife.33660</ref>
Indeed, mPiezo trimer is non-planar conformation inside lipid bilayer, it produces a local dome-shaped deformation of the membrane. In cells, this membrane curvature project towards the cytoplasm and some electrostatics interactions stabilize the trimeric assembly in its curved conformation.<ref name = "nv article"> DOI 10.7554/eLife.33660</ref>
The structure of Piezo1 offers a plausible explanation for the origin of its tension [https://en.wikipedia.org/wiki/Gating_(electrophysiology)gating]. Indeed, if the semi-spherical dome becomes flatter when Piezo1 opens, then the channel membrane system will expand thanks to the flexibility of the blades.
The structure of Piezo1 offers a plausible explanation for the origin of its tension [https://en.wikipedia.org/wiki/Gating_(electrophysiology)gating]. Indeed, if the semi-spherical dome becomes flatter when Piezo1 opens, then the channel membrane system will expand thanks to the flexibility of the blades.
However, because flattening does not constrain the pore to open wide, expansion and pore diameter are decoupled such that Piezo1 can exhibit is small conductance and cation selectivity, properties that are essential to its function.<ref name ="Piezo Senses Tension"/>,<ref name="Fanny"> DOI  10.1038/s41586-019-1499-2</ref>  
However, because flattening does not constrain the pore to open wide, expansion and pore diameter are decoupled, such that Piezo1 can exhibit its small conductance and cation selectivity, properties that are essential to its function.<ref name ="Piezo Senses Tension"/>,<ref name="Fanny"> DOI  10.1038/s41586-019-1499-2</ref>  




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==='''Blade'''===
==='''Blade'''===


Piezo1 has a central domain which is composed of <scene name='86/868186/Cedohihctd_color2/1'>one CTD, one cap (or CED), 3 inner helice (IH) and 3 outer helice (OH)</scene>.
Piezo1 has a central domain which is composed of <scene name='86/868186/Cedohihctd_color2/1'>one CTD, one cap (or CED), 3 inner helices (IH) and 3 outer helices (OH)</scene>.
This central domain is surrounded by 3 extended arms called <scene name='86/868186/Blade/2'>blades</scene> extending out from the central pore in a rotatory manner <ref name ="Alexandra"> Zhou, Z. (2019). Structural Analysis of Piezo1 Ion Channel Reveals the Relationship between Amino Acid Sequence Mutations and Human Diseases. 139–155. DOI 10.4236/jbm.2019.712012 </ref>.
This central domain is surrounded by 3 extended arms called <scene name='86/868186/Blade/2'>blades</scene> extending out from the central pore in a rotatory manner <ref name ="Alexandra"> Zhou, Z. (2019). Structural Analysis of Piezo1 Ion Channel Reveals the Relationship between Amino Acid Sequence Mutations and Human Diseases. 139–155. DOI 10.4236/jbm.2019.712012 </ref>.
"Each of these blades, deflecting at an angle of 100° perpendicular to the membrane, contains 6 tandems transmembranar helical units (THUs) constitute of 4 transmembrane domains".<ref name= "Article six"> DOI 10.1038/nature25743</ref>,<ref name="Alexandra"/> "They are not planar: instead, they lie on a spherically curved surface with the membrane bulging into the cytoplasm".<ref name= "Piezo Senses Tension "> DOI 10.1016/j.cub.2018.02.078</ref>
"Each of these blades, deflecting at an angle of 100° perpendicular to the membrane, contains 6 tandems transmembranar helical units (THUs) constitute of 4 transmembrane domains".<ref name= "Article six"> DOI 10.1038/nature25743</ref>,<ref name="Alexandra"/> "They are not planar: instead, they lie on a spherically curved surface with the membrane bulging into the cytoplasm".<ref name= "Piezo Senses Tension "> DOI 10.1016/j.cub.2018.02.078</ref>