{"id":6294,"date":"2023-02-17T06:54:17","date_gmt":"2023-02-17T06:54:17","guid":{"rendered":"https:\/\/beta.nanion.de\/resource_library\/2019-arg-8-of-yeast-subunit-e-contributes-to-the-stability-of-f-atp-synthase-dimersand-to-the-generation-of-the-full-conductance-megachannel\/"},"modified":"2023-02-17T06:54:17","modified_gmt":"2023-02-17T06:54:17","slug":"2019-arg-8-of-yeast-subunit-e-contributes-to-the-stability-of-f-atp-synthase-dimersand-to-the-generation-of-the-full-conductance-megachannel","status":"publish","type":"resource_library","link":"https:\/\/nanion.com\/zh-hans\/resource_library\/2019-arg-8-of-yeast-subunit-e-contributes-to-the-stability-of-f-atp-synthase-dimersand-to-the-generation-of-the-full-conductance-megachannel\/","title":{"rendered":"2019 &#8211; Arg-8 of yeast subunit e contributes to the stability of F-ATP synthase dimersand to the generation of the full-conductance megachannel"},"content":{"rendered":"<p>The mitochondrial F-ATP synthase is a complex molecular motor arranged in V-shaped dimers that is responsible for most cellular ATP synthesis in aerobic conditions. In the yeast F-ATP synthase, subunits e and g of the FO sector constitute a lateral domain, which is required for dimer stability and cristae formation. Here, by using site-directed mutagenesis we identified Arg-8 of subunit e as a critical residue in mediating interactions between subunits e and g, most likely through an interaction with Glu-83 of subunit g. Consistent with this hypothesis (i) substitution of Arg-8 in subunit e (eArg-8) with Ala or Glu or of Glu-83 in subunit g (gGlu-83) with Ala or Lys destabilized the digitonin-extracted F-ATP synthase, resulting in decreased dimer formation, as revealed by blue-native electrophoresis; and (ii) simultaneous substitution of eArg-8 with Glu and of gGlu-83 with Lys rescued digitonin-stable F-ATP synthase dimers. When tested in lipid bilayers for generation of Ca<sup>2+<\/sup>-dependent channels, wild-type dimers displayed the high-conductance channel activity expected for the mitochondrial megachannel\/permeability transition pore, whereas dimers obtained at low digitonin concentrations from the Arg-8 variants displayed currents of strikingly small conductance. Remarkably, double replacement of eArg-8 with Glu and of gGlu-83 with Lys restored high-conductance channels indistinguishable from those seen in wild-type enzymes. These findings suggest that the interaction of subunit e with subunit g is important for generation of the full-conductance megachannel from F-ATP synthase.<\/p>\n","protected":false},"featured_media":0,"template":"","products_tags":[40],"resource_type":[75],"application_areas":[108],"therapeutic_areas":[],"target_categories":[60],"target_families":[353],"targets":[210],"resource_keyword":[],"class_list":["post-6294","resource_library","type-resource_library","status-publish","hentry","products_tags-orbit-mini","resource_type-publication","application_areas-transporters","target_categories-transporters","target_families-f-type-atpases","targets-fof1-atpase"],"acf":[],"_links":{"self":[{"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/resource_library\/6294","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/resource_library"}],"about":[{"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/types\/resource_library"}],"wp:attachment":[{"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/media?parent=6294"}],"wp:term":[{"taxonomy":"products_tags","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/products_tags?post=6294"},{"taxonomy":"resource_type","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/resource_type?post=6294"},{"taxonomy":"application_areas","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/application_areas?post=6294"},{"taxonomy":"therapeutic_areas","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/therapeutic_areas?post=6294"},{"taxonomy":"target_categories","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/target_categories?post=6294"},{"taxonomy":"target_families","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/target_families?post=6294"},{"taxonomy":"targets","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/targets?post=6294"},{"taxonomy":"resource_keyword","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/resource_keyword?post=6294"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}