A^pN̕q@\̍\

<strong>G  </strong>
iww@wn wUj
emailF<a href="mailto:nureki@biochem.s.u-tokyo.ac.jp">G </a>
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̈Zr[, <strong>2</strong>, e009 (2013)@<a href="http://dx.doi.org/10.7875/leading.author.2.e009">DOI: 10.7875/leading.author.2.e009</a>
Osamu Nureki: <strong>Structural basis for molecular mechanism of membrane channels and transporters.</strong>

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<h2>v </h2>
@זE͐1qʂȂdCȂ킿CזEɂ肨ĂCזE͍זE̓O̊u邱ƂɂזE̓𐶖ɓKɈێĂDɖߍ܂ꂽ`l▌A^pŃCזE̓ÕCICCӎYC邢́C򕨂Ȃǂٕ̈𐳊mɗA邱ƂɂC̍זE̊ێim}VłDqg̈`q30ȏ͖^pNR[hĂCn^[Qbg50ȏ͖^pNł邱ƂC^pŇ͐̒T݂̂Ȃ炸Cւ̉pɂ߂ďdvłDŋ߂ɂȂCR̂yv`hƂqoC_[pēIȖ^pN̍\艻PZpCɂČsL[rbN@̋ZpCVNg̃}CNtH[JXXr[p\ȍ\͂̋ZpȂǁCՂƂȂZpiC`l▌A^pNǂ̂悤ɓٓIȗAFCǂ̂悤ɗA쓮Cǂ̂悤ɗA𐧌䂵Ă̂CȂǁCq@\̉𖾂Iɐi񂾁Dł́C`lіA^pN̕q@\̍\ՂɂāCŋ߂̒m܂D

<h2>͂߂</h2>
@זE͍זE̓ŐE߁CזE̓O̊Ƃ͈قȂԂňێCזE̐ɂƂsȖ͂DזE̓OɗA邱Ƃɂ肱̈قȂ肾Ă̂CזEɖߍ܂ꂽ`l▌A^pNłD`ĺCAꎩ̂̂w|eVGlM[idCwIȌzjɂA쓮̂ŁĈ悤ȗA͎󓮗AƂ΂DAɑ΂ea͒ႭC̕CȂx͔ɑDɑ΂āCA^pŃCAƂ̌ɂƂȂ\ωNƂɂAs߁CȂx͒xD̃`lіA^pN@\ɂdvȓ_́C1j̋@\̖{łgA̋쓮@\hC2jA̎ʋ@\C3jA̐@\CłDȂCA^pN܂ޖ^pN͎̒Ȃǂ̖肩痧̍\̌肪łC̗͂ꂽ󋵂ɂD̈Cŋ߂ɂȂCɓK^pNvɃXN[jOuoQ߃N}gOtB[@ifluorescence-detection exclusion size chromatographyFFESCj̋ZpCR̂yv`hƂgqoC_[hpēIȖ^pN̍\艻PZpCɂČsL[rbN@ilipidic cubic phaseFLCPj̋ZpȂǁC^pN̍\ȍ\͂̂߂̋ZpIɐiCɂ3̓_͉𖾂Dł́C3̓_ɏœ_ĂȂC`lіA^pN̕q@\D

<h2>1D`lɂA̎ʋ@\</h2>
@K<sup>+</sup>`ĺCCIa1.51K<sup>+</sup>͓߂邪C1.16ƂCIȁNa<sup>+</sup>͒ʂȂD`lPȂEłȂC傫̂ʂȂ菬̂ʂ͂łD̓𖾂̂Roderick MackinnonŁČтɂ2003NɃm[xw܂܂D
@MackinnońCK<sup>+</sup>`lKcsǍ\\Ō肵<a href="#R1"><sup>1)</sup></a>ĎʁCזE̊O̓̕t߂ɁCyv`h卽̃J{j_fThr̃_f5cɕсCꂪlʑ̂Ƃ4Ώ̂Ő񂵂CI̒ʂ蓹\Ăi<a href="#F1">}1</a>jDׂƂɁCʏCK<sup>+</sup>͐q8zʂĂ̂ɑ΂C̍\ł͂4EaĂ̎_fqɂuĂDK<sup>+</sup>̓CIa\ɑ傫̂Ŏ_fqɂzʌɌ`CEaɂ艻GlM[̌EDɑ΂CNa<sup>+</sup>̓CIaC_fqɂȔzʌ`łȂߒEaN炸CނCa傫Ȃ肱̃CI̒ʂ蓹ʉ߂łȂƂꂽD̂߁C̃CI̒ʂ蓹̓CII𐫃tB^[iion selectivity filterjƖꂽD

<a name="F1"></a><div id="fig1-caption-text" style="display: none;"><strong>}1@K<sup>+</sup>`lKcsÂCII𐫃tB^[</strong>
iaj݂ƂD
ibjזE̊O݂ƂD
K<sup>+</sup>iF̋jזE̊OւƏoĂƂCyv`h卽̃J{j_fqɂzʂEa邱ƂɂNa<sup>+</sup>ƎʂDKcsA͎lʑ̂Ƃ邱ƂɂC̃CII𐫃tB^[`ĂD
[PDB IDF<a href="http://service.pdbj.org/mine/Detail2?PDBID=1k4c&PAGEID=Summary" target="_blank">1K4C</a>C<a href="http://service.pdbj.org/mine/Detail2?PDBID=1k4d&PAGEID=Summary" target="_blank">1K4D</a>]
<a href="http://leading.lifesciencedb.jp/wordpress/wp-content/uploads/2013/09/Nureki-2.e009-Fig.1.jpg" target="_blank">[Download]</a></div>[hs_figure id=1&amp;image=/wordpress/wp-content/uploads/2013/09/Nureki-2.e009-Fig.1.png&amp;caption=fig1-caption-text]


<h2>2D`lɂA̐@\</h2>
@Mg<sup>2+</sup>̓CIa0.72ł̂ɑ΂CqƂ̐eaߐaa5.3Ɣɑ傫CCo<sup>2+</sup>Ni<sup>2+</sup>ɋ߂DAJyދCa<sup>2+</sup>̓CIa1.12Caa2.9łCaɂ蔼a͂܂ςȂDMg<sup>2+</sup>͎_fqƂ̐ea߁C_yf|[[ȂǂATPaseG^pNȂGTPase̕yfƂĂ͂炭DזECa<sup>2+</sup>Zx͍זȄԂɑ傫ȉeyڂƂmĂ邪Cŋ߁CזEMg<sup>2+</sup>ZxُɂȂƁCSaCAaCȂǐKaN邱ƂCMg<sup>2+</sup>זẼzIX^VXɏdvȖ͂ĂƂ炩ɂȂĂD܂Cŋ߁CMg<sup>2+</sup>͔]ɂL̕ێɂdvł邱Ƃ<a href="#R2"><sup>2)</sup></a>i<a href="http://first.lifesciencedb.jp/archives/5151" target="_blank">V_r[</a> łfځjD
@M҂́CזE̊OւMg<sup>2+</sup>̎荞݂SVKMg<sup>2+</sup>A^pNMgtEɂāCMg<sup>2+</sup>݉ɂ\X\͂ɂ2.9𕪉\Ō肵<a href="#R3"><sup>3,4)</sup></a>i<a href="#F2">}2</a>jĎʁCMgtE̖ђʃhCɁĈ̓OւMg<sup>2+</sup>𓧉߂邽߂́gCIߍEhזE؂邩ő݂邱Ƃ炩ɂȂD̃CIߍEɂ́CA̓rɂƍlMg<sup>2+</sup>l̓dqxϑꂽDCMg<sup>2+</sup>ߏɂMgtE̍\ł́C5Ԗڂ̖ђʃwbNXɂMg<sup>2+</sup>̓ߍEӂĂi<a href="#F2">}2</a>jDɁCehC̋Eɂ͑̎_A~m_cтĂCMg<sup>2+</sup>Ɍēdׂ𒆘aĂ邱ƂDɁCMgtE̍\ɂāgMg<sup>2+</sup>ZT[hƂċ@\ƍlזEhCɂāCMg<sup>2+</sup>ߏ邢Mg<sup>2+</sup>Rꂼɂ闧̍\肵ĎʁCMg<sup>2+</sup>RɂזEhC̍\ɂ́CehC݂ɔĊJ悤ȑ傫ȍ\ω݂ꂽDזEMg<sup>2+</sup>ZxɈˑ̍\ώCRs[^[pq͊wV~[VɂĂČꂽ<a href="#R5"><sup>5)</sup></a>D̍זEhC̍\ωђʃhC̍\ωUNCCIߍEJMg<sup>2+</sup>̓߂𐧌䂷ƐꂽDȏӂ܂CMgtE̍זEhCזEMg<sup>2+</sup>Zxm邱ƂɂCMg<sup>2+</sup>ߏȂƂɂMg<sup>2+</sup>荞݂jQCRĂꍇɂMg<sup>2+</sup>荞݂𑣐iƂCMg<sup>2+</sup>oXێ̕q@\񏥂<a href="#R3"><sup>3)</sup></a>i<a href="#F3">}3</a>jDɁCdCwȉ͂ɂCMgtEMg<sup>2+</sup>ɓٓIȃ`lłCזEMg<sup>2+</sup>ZxɈˑăCIߍEJ邱Ƃ؂<a href="#R4"><sup>4)</sup></a>D[ƂɁCזEhCMg<sup>2+</sup>ƌcɕψق𓱓MgtEψّ̂ł́CMg<sup>2+</sup>ZxɂĂCIߍE͊JςȂɂȂĂCזEhCƃCIߍE̊J͂ق100ɂȂƂCMgtE̍זEhCMg<sup>2+</sup>ZT[ƂĂ͂炫CCIߍE̊J𐧌䂷邱ƂɂזEMg<sup>2+</sup>Zx𐧌䂵Ă邱Ƃ؂ꂽ<a href="#R4"><sup>4)</sup></a>D
@܂ŋ߂ɂȂCM҂́CMgtE̖ђʃhCL[rbN@ɂ茋C2.3𕪉\ō\肵ĎʁCMg<sup>2+</sup>͐ʑ̌^̘Za\̂܂MgtE̓A邱Ƃ킩CKcsȀꍇƂ͈قȂCSȐaԂ̑傫ȐaaF邱Ƃɂق̗zCIƂ͎ʂCVK̎ʋ@\炩ɂȂD

<a name="F2"></a><div id="fig2-caption-text" style="display: none;"><strong>}2@Mg<sup>2+</sup>`lMgtE̍\ƃCIߍE</strong>
iajŜ̍\D
ibjђʕg債ƂD
זEhCMg<sup>2+</sup>ZT[ƂĂ͂炫CזEMg<sup>2+</sup>ƃCIߍE\ɂił́C\jD
<a href="http://leading.lifesciencedb.jp/wordpress/wp-content/uploads/2013/09/Nureki-2.e009-Fig.2.jpg" target="_blank">[Download]</a></div>[hs_figure id=2&amp;image=/wordpress/wp-content/uploads/2013/09/Nureki-2.e009-Fig.2.png&amp;caption=fig2-caption-text]

<a name="F3"></a><div id="fig3-caption-text" style="display: none;"><strong>}3@MgtEɂזEMg<sup>2+</sup>̃zIX^VX̋@\</strong>
iajזEMg<sup>2+</sup>ߏȂƂD
ibjזEMg<sup>2+</sup>RĂƂD
<a href="http://leading.lifesciencedb.jp/wordpress/wp-content/uploads/2013/09/Nureki-2.e009-Fig.3.jpg" target="_blank">[Download]</a></div>[hs_figure id=3&amp;image=/wordpress/wp-content/uploads/2013/09/Nureki-2.e009-Fig.3.png&amp;caption=fig3-caption-text]


<h2>3DA^pNɂ\A</h2>
@A^pN͗Aɑ΂1ȏ̓ٓIȌʂČʂזE̊OɘIoɘIo肷tIȍ\ωNʁCA͍זEʉ߂DA^pNł̓GlM[ƋėAdCwIȌzɋt炢\ÂقƂǂłDA^pŃC\A쓮GlM[ɂCȉ3ɕނD1j<strong>A^pN</strong>icoupled transporterjFzɋtA̗ACzɂʂ̗A̗AƋD2j<strong>ATP쓮^|v</strong>iATP-driven pumpjFATP̉ƗA̔\AƂD3j<strong>쓮^|v</strong>ilight-driven pumpjFGlM[̎eƗA̔\AƂ̂ŁCɍ׋ۂÍ׋ۂ̃hvVt@~[^pND
@A^pNɂāC2̗A̗Â̕V|[gCt̂̂A`|[gƂD@CIdCwIȌzɂĈړۂɕo鎩RGlM[CЂƂ̗AA邽߂̋쓮͂ƂėpꍇDƂɁC̍זEłNa<sup>+</sup>̓dCwIȌz傫ȋ쓮͂ƂȂĂDčזEɗꍞNa<sup>+</sup>́CŁCזEɑ݂ATP쓮^|vłNa<sup>+</sup>|vɂזEOɂݏoDATP쓮^|v́CNa<sup>+</sup>̓dCwIȌz`邱ƂɂԐړIɗA̗A쓮Ă邱ƂɂȂD̂߁ĈƂCATP쓮^|v1A^pNCA^pN2A^pNƂԁD
@Ƃ΁Ct̏זEł́CdCwIȌzɂėNa<sup>+</sup>ƋāCA~m_זEɗAiV|[gjD̏ꍇCA^pN\ωNčזEOJ\זEJ\ƂȂ̂́C̗AiNa<sup>+</sup>Ɠ邢̓A~m_jƌƂCƂĂȂƂ݂̂łDC׋ۂył́C\Ȃ唼Na<sup>+</sup>ł͂ȂH<sup>+</sup>̌zɈˑĂCזẼIKlƎĂD́CזENa<sup>+</sup>|vقƂǂȂH<sup>+</sup>|vłDH<sup>+</sup>̓dCwIȌzɂ쓮V|[gɂċA^pNƂČÂ猤Ă̂ɁCNg[XߍyfLacYD

<h2>4DLacYɂV|[g̋@\</h2>
@LacYMFSimajor facilitator superfamilyjƂ12񖌊ђʃ^pNX[p[t@~[ɑDMFSH<sup>+</sup>ƗAV|[g鋤A^pNłC1000ȏ̃t@~[Ȃ閌A^pNƂĂ͍ő̃X[p[t@~[łDLacYɂĂX\͂ɂA̌זEJ\̍\񍐂ĂC̃V|[g̋@\炩ɂĂ<a href="#R6"><sup>6)</sup></a>i<a href="#F4">}4</a>jDLacY12{̖ђʂփbNX6{2̃[u`ĂCזEOJ\ł́CN[̃[uɑ݂Arg144Glu126ƂÓdݍpɂ茋Ă邽߁CC[̃[uGlu269RɂȂH<sup>+</sup>ƌD̂߁CN[̃[u̓dCIɒaꂽ|PbgɗAł郉Ng[Xł悤ɂȂDLacYזEJ\ɕςArg144Glu269ƌ悤ɂȂCH<sup>+</sup>ÔƓɖђʂփbNXׂ悤ɍ\ωNCNg[XƂ̌ʂ͉ăNg[X͍זEւƕoDA^pN\ωN̗̂͗AƂƂĂȂƂ݂̂łCH<sup>+</sup>ƌԂ̂ō\ω͋NȂ̂ŁCH<sup>+</sup>̓Ng[XƂƂɂAȂD

<a name="F4"></a><div id="fig4-caption-text" style="display: none;"><strong>}4@LacYɂH<sup>+</sup>ƃNg[X̃V|[g̋@\</strong>
iajLacY̍זE\ƍזEJ\D
ibjH<sup>+</sup>ƃNg[X̃V|[g̋@\DH<sup>+</sup>݂̂2̏Ԃ̂ł̍\ω͋NȂ̂ŁCH<sup>+</sup>̓Ng[XƂƂɗAD
<a href="http://leading.lifesciencedb.jp/wordpress/wp-content/uploads/2013/09/Nureki-2.e009-Fig.4.jpg" target="_blank">[Download]</a></div>[hs_figure id=4&amp;image=/wordpress/wp-content/uploads/2013/09/Nureki-2.e009-Fig.4.png&amp;caption=fig4-caption-text]


<h2>5DPOTɂV|[g̋@\</h2>
@POTMFSɑ鋤A^pNŁCH<sup>+</sup>ƃWyv`h邢̓gyv`hV|[gDqgł͏OтPepT1PepT2ƂPOTʂɔĂC^pNĂłyv`h̎荞݂ɂ͂炢Ă<a href="#R7"><sup>7)</sup></a>DɁCPOT̓N^n̍RRECX܂Ȃǂ̖܂̎荞݂ɂ͂炢ĂC̕ɂĂdvł<a href="#R8"><sup>8)</sup></a>D
@M҂́CL[rbN@pɂCPOTPƁCсCPOTƗAłWyv`hAiOƂ̂̌̕\1.9`2.5𕪉\Ƃ\Ŗ炩ɂ<a href="#R9"><sup>9)</sup></a>i<a href="#F5">}5</a>jD̍\͍זEJ\łCPOTArg43ƃvgꂽGlu310ivgꂽƂ̂݁CdCIȔȂfłjAłWyv`h̃J{LV𐅑fɂFĂ邱Ƃ킩i<a href="#F5">}5</a>jDɁCRs[^[pq͊wV~[Vɂ͂CGlu310EvgƓdCIȔɂWyv`hłȂȂCCArg43Glu310ƂÓdݍpňčזEJ\זE\ւƕω邱Ƃ炩ɂȂD́CזEJ\ɂėAłWyv`h𗣂זE\ւƕω鐶IȉߒɑD܂CRs[^[V~[VɂCH<sup>+</sup>ƃWyv`hƂƂC邢́CĂȂƂ̂ݍ\ωNCH<sup>+</sup>݂̂̌Ԃł͍\ω͋NȂƂCV|[g̎vȕq@\̍\Ղ𖾂邱Ƃł<a href="#R9"><sup>9)</sup></a>DȂ킿C|Pbg̕\ʂ̓d׏ԂGlu310̃vgɂ蒆a邱ƂɂAłWyv`hCH<sup>+</sup>̗AƂƂɃWyv`h𗣂ăV|[g̋N邱Ƃ炩ɂȂD

<a name="F5"></a><div id="fig5-caption-text" style="display: none;"><strong>}5@POTƗA̃AiOƂ̂̌̕\</strong>
iajŜ̍\D
ibjʂg債ƂD
A̃AiOƂăAtzXt@pDGlu310vg邱ƂɂAƌł悤ɂȂDזEJ\łArg43Glu310ƐÓdݍp邱ƂɂH<sup>+</sup>͉𗣂CA𗣂D
[PDB IDF<a href="http://service.pdbj.org/mine/Detail2?PDBID=4ikz&PAGEID=Summary" target="_blank">4IKZ</a>]
<a href="http://leading.lifesciencedb.jp/wordpress/wp-content/uploads/2013/09/Nureki-2.e009-Fig.5.jpg" target="_blank">[Download]</a></div>[hs_figure id=5&amp;image=/wordpress/wp-content/uploads/2013/09/Nureki-2.e009-Fig.5.png&amp;caption=fig5-caption-text]


<h2>6DMATEɂA`|[g̋@\</h2>
@MATEimultidrug and toxic compound extrusionj͑ܔroA^pNłCNa<sup>+</sup>邢H<sup>+</sup>̃C|[gƋ邱ƂɂCٕ₳܂܂Ȗ܂A`|[gɂזE̊OւƔro<a href="#R10"><sup>10)</sup></a>DqgMATE͐t̑ɂđĂCזËٕ̔roɏdvȖ͂Ă<a href="#R11"><sup>11)</sup></a>DCa׋ۂ₪זEɂMATEʂɔƁCRR܂̌ȂܑϐۂRܑϐזEo邱ƂɂȂ邽߁CMATȆjQ܂̊J͈̕ɂċ}ƂȂĂ<a href="#R12"><sup>12)</sup></a>D
@M҂́CH<sup>+</sup>ɂ쓮Í׋ۂMATĚ\CPƁCсCR邢͑jQyv`hƂ̂̂̕2.1`3.0𕪉\Ƃ\Ō肵<a href="#R13"><sup>13)</sup></a>i<a href="http://first.lifesciencedb.jp/archives/6953" target="_blank">V_r[</a> łfځjDMATEMFSƂ悭ĂC12{̖ђʂփbNX6{2̃wbNXohhC`ĂāCזEOJ\ƂĂi<a href="#F6">}6</a>jDMATE͒PƂłCꂽƂpHɂ2̍\Ƃ邱Ƃ킩D̕t߂ł̓wbNX1܂LтƂCXg[g\ƖꂽDC_ł̓wbNX1͐^񒆂Pro26ɂĐ܂ȂC傫Ȃxg\ƂD̃xg\ł́CwbNX1ɂ|PbgӂCAƂȂ܂͌łȂƂ킩DɁC|PbĝN[hĈɂAsp41Asp184Ȃǂ̎_A~m_c邢͐eA~m_cCXg[g\ɂĂ͂邭ĂC_łAsp41vg邱ƂɂAsp184ȂǂƋłȐflbg[N`CwbNX1荞ނƂɂxg\ɂȂAro邱Ƃ炩ɂȂDȏ̂ƂCH<sup>+</sup>Ƌ܂̔ro@\炩ɂȂ<a href="#R13"><sup>13)</sup></a>i<a href="#F7">}7</a>CURĹC<a href="http://www.nature.com/nature/journal/v496/n7444/fig_tab/nature12014_SV1.html" target="_blank">http://www.nature.com/nature/journal/v496/n7444/fig_tab/nature12014_SV1.html</a>jDɁCMATEƋłɌyv`hXN[jOƂĈЂƂ͖܌|Pbg苒i<a href="#F6">}6</a>jCjQƂ킩C܂Ŗ܂roĂ܂ߑjQ܂fUC邱Ƃs\łMATEɑ΂CjQ܂̊J铹JƂɂȂ<a href="#R13"><sup>13)</sup></a>D

<a name="F6"></a><div id="fig6-caption-text" style="display: none;"><strong>}6@MATĚ\</strong>
iajRmtLTVƂ̂̍̕\D[PDB IDF<a href="http://service.pdbj.org/mine/Detail2?PDBID=3vvp&PAGEID=Summary" target="_blank">3VVP</a>]
ibjjQyv`hMAD5Ƃ̂̍̕\D[PDB IDF<a href="http://service.pdbj.org/mine/Detail2?PDBID=3vvr&PAGEID=Summary" target="_blank">3VVR</a>]
<a href="http://leading.lifesciencedb.jp/wordpress/wp-content/uploads/2013/09/Nureki-2.e009-Fig.6.jpg" target="_blank">[Download]</a></div>[hs_figure id=6&amp;image=/wordpress/wp-content/uploads/2013/09/Nureki-2.e009-Fig.6.png&amp;caption=fig6-caption-text]

<a name="F7"></a><div id="fig7-caption-text" style="display: none;"><strong>}7@MATEɂA`|[g̋@\</strong>
2̃[učזEOJ\ƍזEJ\Ƃ̂s邱ƂɂAAƍlĂD̂C\̌肪ȂĂ͍̂זEOJ\łDזEOJ\ւ̍\ωł͊|Pbg̗A̔ro͊CAsp41̃vgƂȂ|PbgC^pN̓Aǂo邱ƂŁC̗ATCNɂނƍlꂽD
<a href="http://leading.lifesciencedb.jp/wordpress/wp-content/uploads/2013/09/Nureki-2.e009-Fig.7.jpg" target="_blank">[Download]</a></div>[hs_figure id=7&amp;image=/wordpress/wp-content/uploads/2013/09/Nureki-2.e009-Fig.7.png&amp;caption=fig7-caption-text]


<h2>7DCAXɂCa<sup>2+</sup>H<sup>+</sup>̃A`|[g̋@\</h2>
@^j̍זE1 mMقǂ̍Ca<sup>2+</sup>Zx̊ɂ炳ȂCזEɂVCa<sup>2+</sup>Zx0.1Mxɂ܂ŉ邱ƂɂCCa<sup>2+</sup>̗ɂזEVOi`BiƂ΁Cؓ̎kjBĂDāCזECa<sup>2+</sup>ZxႭۂA^pN͐̈ێɂƂ肫߂ďdvłDCa<sup>2+</sup>זEOɔro邨ȗA^pNɂ́CqP^Ca<sup>2+</sup>|vƁCCa<sup>2+</sup>/zCIA^pNƂ<a href="#R14"><sup>14)</sup></a>DCa<sup>2+</sup>/zCIA^pN̋@\sS̓qgɂčN邱ƂmĂD
@M҂́CH<sup>+</sup>/Ca<sup>2+</sup>A^pNCAX̌\2.3𕪉\Ō肵ĎʁCCAX̓RAhCƃQ[eBOoh\邱Ƃ炩ɂȂ<a href="#R15"><sup>15)</sup></a>i<a href="http://first.lifesciencedb.jp/archives/7281" target="_blank">V_r[</a> łfځji<a href="#F8">}8</a>jDłɕ񍐂ĂNa<sup>+</sup>/Ca<sup>2+</sup>A^pN̍\זEOJ\ł̂ɑ΂<a href="#R16"><sup>16)</sup></a>CCAX̍\͍זEJ\łD2̍\̔rCCa<sup>2+</sup>/zCIA^pN̓Q[eBOohRAhC̕\ʂɂapb`̂邱ƂɂQ[eBOփbNX]Ĉɑ݂eNX^[זE̊O̓ߍECזE̓ߍE肱ƂԂƂɂCזEOJ\ƍזEJ\Ƃ̂؂ւ邱Ƃ炩ɂȂ<a href="#R15"><sup>15)</sup></a>i<a href="#F8">}8</a>jD܂C̍\ł́C3̃O^~_cGlu78CGlu255CGlu258݂ɂ邢̓O^~cƐf`ĂƂvgԂłCzCI|Pbg3H<sup>+</sup>H<sup>+</sup>^łƍlꂽi<a href="#F9">}9</a>jDCCa<sup>2+</sup>^Na<sup>+</sup>/Ca<sup>2+</sup>A^pN̍\Ɣr邱ƂɂC̃vgĂ3GlûGlu78Glu258ςCa<sup>2+</sup>ƌ邱Ƃi<a href="#F9">}9</a>jCH<sup>+</sup>Ca<sup>2+</sup>͓ɂ͌łȂƂ킩DɁCzCI|PbgH<sup>+</sup>Ca<sup>2+</sup>邱ƂɂC͂߂ăRAhCɑapb``CQ[eBOoh͂̂邱Ƃ̂ł悤ɂȂ邱Ƃ炩ɂȂCzCIɈˑIȍ\ω̋@\𖾂ꂽ<a href="#R15"><sup>15)</sup></a>iURĹC<a href="http://www.sciencemag.org/content/suppl/2013/05/23/science.1239002.DC1/1239002s1.mov" target="_blank">http://www.sciencemag.org/content/suppl/2013/05/23/science.1239002.DC1/1239002s1.mov</a>jD

<a name="F8"></a><div id="fig8-caption-text" style="display: none;"><strong>}8@CAX̌\</strong>
[PDB IDF<a href="http://service.pdbj.org/mine/Detail2?PDBID=4kpp&PAGEID=Summary" target="_blank">4KPP</a>]
<a href="http://leading.lifesciencedb.jp/wordpress/wp-content/uploads/2013/09/Nureki-2.e009-Fig.8.jpg" target="_blank">[Download]</a></div>[hs_figure id=8&amp;image=/wordpress/wp-content/uploads/2013/09/Nureki-2.e009-Fig.8.png&amp;caption=fig8-caption-text]

<a name="F9"></a><div id="fig9-caption-text" style="display: none;"><strong>}9@H<sup>+</sup>/Ca<sup>2+</sup>A^pNCAXNa<sup>+</sup>/Ca<sup>2+</sup>A^pN̗zCI|Pbg̔r</strong>
iajH<sup>+</sup>/Ca<sup>2+</sup>A^pNCAXD[PDB IDF<a href="http://service.pdbj.org/mine/Detail2?PDBID=4kpp&PAGEID=Summary" target="_blank">4KPP</a>]
ibjNa<sup>+</sup>/Ca<sup>2+</sup>A^pND[PDB IDF<a href="http://service.pdbj.org/mine/Detail2?PDBID=3v5u&PAGEID=Summary" target="_blank">3V5U</a>]
<a href="http://leading.lifesciencedb.jp/wordpress/wp-content/uploads/2013/09/Nureki-2.e009-Fig.9.jpg" target="_blank">[Download]</a></div>[hs_figure id=9&amp;image=/wordpress/wp-content/uploads/2013/09/Nureki-2.e009-Fig.9.png&amp;caption=fig9-caption-text]

@ȏCMATECAX̍\@\͂̌ʁC2̗A̂ǂ炩Ƃ̂݁CזEOJ\ƍזEJ\Ƃ̂̍\ωUNCAAƂCA`|[g̎vȕq@\̍\Ղ炩ɂȂi<a href="#F10">}10</a>jD

<a name="F10"></a><div id="fig10-caption-text" style="display: none;"><strong>}10@CAXɂA`|[g̋@\</strong>
CAXCa<sup>2+</sup>邢H<sup>+</sup>Ƃ̂݁CזEOJ\ƍזEJ\Ƃ̂̍\ωND
<a href="http://leading.lifesciencedb.jp/wordpress/wp-content/uploads/2013/09/Nureki-2.e009-Fig.10.jpg" target="_blank">[Download]</a></div>[hs_figure id=10&amp;image=/wordpress/wp-content/uploads/2013/09/Nureki-2.e009-Fig.10.png&amp;caption=fig10-caption-text]


<h2>8DATP쓮^|v</h2>
@ATP쓮^|vATPADPƃ_ւ̉ɂ萶GlM[𗘗p邽߁CAATPaseƂ΂DATP쓮^|vɂ͂3̌^D
@1j<strong>P^|v</strong>iP-type ATPasejFATCN̂ɗA^pN̂_̂P^Ƃ΂DזE͂Na<sup>+</sup>CK<sup>+</sup>CH<sup>+</sup>CCa<sup>2+</sup>Ȃǂ܂܂ȗzCǏz`CI|v܂܂D
@2j<strong>F^|v</strong>iF-type ATPasejF̃Tujbg\^[r̂悤Ȃ|vłDF^|vɂF^ATPaseV^ATPaseƂD׋ۂ̍זEC~gRhA̓CtΑ̂̃`RChɂ݂DF^ATPasȇ͖͂H<sup>+</sup>̔ZxzɂADPƃ_ATP邪C̋tG}邽ATPyfƂ΂DH<sup>+</sup>̔ZxźCDC׋ۂ~gRhAł͎_I_ɂƂȂdq`BɂCtΑ̂ł͌ɂCDۂł̓oNeIhvV̂悤Ȍ쓮^H<sup>+</sup>|vɂC`DC\\[CVivXECẢtEȂǂ̃IKlɂ́CATPςH<sup>+</sup>|vƂăIKlpHႭۂ߂ɂ͂炭V^ATPaseD܂ł̂ƂCF^ATPaseɊւĂ͍זEhCł郿Tujbĝقɂ́CђʃhCłcTujbg̃O\񍐂Ă̂ɑ΂<a href="#R17"><sup>17)</sup></a>CV^ATPaseɊւĂ̓[^[hC̍\񍐂Ă<a href="#R18"><sup>18)</sup></a>i<a href="http://first.lifesciencedb.jp/archives/6593" target="_blank">V_r[</a>łfځjD
@3j<strong>ABCA^pN</strong>iABC transporterjFCIAP^|v邢F^|vƂ͈قȂCATP̉̃GlM[A^pN̍\ωƋ邱ƂɂCזE؂ďqADזEATPƌABCiATP-binding cassetteCATPJZbgjhC߂̖DABChC͓ʑ̂`ATPƌĂ邪CATPƓʑ̍\ŃQ[gJ߁CAsĎ\񍐂Ă邪Cŋ߂ł́Cr^~B<sub>12</sub>A^pN̍\񍐂Ă<a href="#R19"><sup>19)</sup></a>D

<h2>9DP^Ca<sup>2+</sup>|vɂCa<sup>2+</sup>̗A@\</h2>
@ɏqׂ悤ɁC^j̍זE̓OCa<sup>2+</sup>ZxzCa<sup>2+</sup>זE̊OւƔ\ACa<sup>2+</sup>|v2A^pNɂێĂāCCa<sup>2+</sup>|v̂ЂƂP^Ca<sup>2+</sup>-ATPasełCЂƂNa<sup>+</sup>̓dCwIȌz쓮Na<sup>+</sup>-Ca<sup>2+</sup>A^pNiNa<sup>+</sup>-Ca<sup>2+</sup> exchangerjłDP^ATPasêƂił̂́Ci؍זE̋؏E̖ɑ݂Ca<sup>2+</sup>-ATPasełSRCA1łD؏ÊCa<sup>2+</sup>̒ɂłCdʂɂ؍זEEɂCa<sup>2+</sup>؏ÊCa<sup>2+</sup>`lʂčזEւƕoCؓkDCa<sup>2+</sup>|v͋؏Ê̖^pN̖90߁CזE؏ÊւCa<sup>2+</sup>\AD
@܂܂ȗȀԂɂSRCA1̍\́CL ߂Poul Nissenɂ𖾂ꂽ<a href="#R20"><sup>20-27)</sup></a>DP^ATPase10{̖ђʂփbNXĈ3{͎dт̃`l̕ǂ`Ăi<a href="#F11">}11</a>jDזEhCATPhCC_hCC쓮hC3̃hCȂCATPƓɁC_hCAsp351_DCa<sup>2+</sup>|v烊_OƁC2{̖ђʂփbNX̍\ŋ؍זE̍זEɂނ󓴂C2Ca<sup>2+</sup>DɁCזEATPhCATPCꂪĐ_Asp351Ɍi_jƁC̃_ƍ쓮hCƂÓdIɑݍp邽߁CɈ3{̖ђʃhC̔zςCCa<sup>2+</sup>ʂ͕󂵂ċ؏Ê̓oɂނJCCa<sup>2+</sup>͏Ê̓oւƕoD

<a name="F11"></a><div id="fig11-caption-text" style="display: none;"><strong>}11@SRCA1ɂATP̉ƋCa<sup>2+</sup>̗A@\</strong>
<a href="http://leading.lifesciencedb.jp/wordpress/wp-content/uploads/2013/09/Nureki-2.e009-Fig.11.jpg" target="_blank">[Download]</a></div>[hs_figure id=11&amp;image=/wordpress/wp-content/uploads/2013/09/Nureki-2.e009-Fig.11.png&amp;caption=fig11-caption-text]


<h2>10D쓮CI`l̕q@\</h2>
@ɁC\AsA^pN3ڂ͌쓮^|vłƏqׂD͂Ɍj̃hvVt@~[^pNłDƂ낪C^j̃hvVt@~[^pŃC|vł͂ȂChvV̂悤G^pNêłCȉɏqׂ悤ȃ`lł肷DߔNC]_oȊw̕ɂāC`lhvVƂ΂쓮^̗zCI`l𗘗pj[̑IIȊ̋ZprтĂD`lhvV͐FeƃCIߍEJNa<sup>+</sup>Ca<sup>2+</sup>ƂzCI𓧉߂邽<a href="#R28"><sup>28)</sup></a>C`lhvVj[ɐFƎ˂邱ƂɂC̃j[݂̂IIɊ邱Ƃ\ɂȂDŋ߁Cɍׂ̌t@Co[]ɑ}邱ƂɂC}EX̂悤ȍł<em>in vivo</em>ɂē̃j[C̃j[邢͐_oHsɂe͂邱Ƃł悤ɂȂ<a href="#R29"><sup>29)</sup></a>D
@M҂́CEɂCL[rbN@pă`lhvV̌ɐČ\2.3𕪉\Ō肵<a href="#R30"><sup>30)</sup></a>i<a href="http://first.lifesciencedb.jp/archives/4321" target="_blank">V_r[</a> łfځji<a href="#F12">}12</a>jD`lhvV͓ʑ̂`ĂCꂼ̃Tujbg蕉̓dו\ʂEĂDۂɁC̍E̓̐eA~m_cɕψق𓱓CdCwȉ͂ɂd𑪒肷邱ƂɂC̍ECIߍEł邱ƂD̃CIߍÉCe郌`i[iʏ͑S<em>trans</em>^ł邪Ce13-<em>cis</em>^ƂȂjVbtɂLys296ɋLĂߖTɑ݂DC̃CIߌ͂̍זE2̃Q[gɂӂĂDȂ킿C̍\͕\iԁj̍\łD̃Q[ǵCGlu122Glu129ꂼHis173CAsn297Ɛf邱ƂɂCIߍEӂłD2GluAlaɒuĂdɕῶȂ̂ɑ΂C˂ɃvgGlu͕킷Glnɒuƌd͑傫ނƂCGlũvgђEvg`l̊Jɏdvł邱ƂꂽDɁCGlu122Glu129EvgԂɂC`i[13-<em>cis</em>^ɂĕq͊wV~[VsƂɂCƎ˂ɂ`l\J\ɕω@\𖾂邱ƂɐDC̍\ɂƂÂĂLpȃ`lhvVψّ̂fUC邱ƂɂC_ow_oaw̕ɑ傫v邱Ƃ҂D

<a name="F12"></a><div id="fig12-caption-text" style="display: none;"><strong>}12@`lhvVƑS<em>trans</em>^`i[Ƃ̂̌̕\</strong>
iaj݂ƂD
ibjזE̊O݂ƂD
ATRFS<em>trans</em>^`i[D
[PDB IDF<a href="http://service.pdbj.org/mine/Detail2?PDBID=3ug9&PAGEID=Summary" target="_blank">3UG9</a>]
<a href="http://leading.lifesciencedb.jp/wordpress/wp-content/uploads/2013/09/Nureki-2.e009-Fig.12.jpg" target="_blank">[Download]</a></div>[hs_figure id=12&amp;image=/wordpress/wp-content/uploads/2013/09/Nureki-2.e009-Fig.12.png&amp;caption=fig12-caption-text]


<h2>11DSecgXR̂ɂ^pN̖</h2>
@܂ŁCCIⓜCyv`hƂq̖A̕q@\ɂďqׂĂDȂC1q߂邱Ƃ̂łȂdC^pN̂悤ȋȕq߂邱ƂłDɂ͂炭A^pNSecgXR̂łDۂɁC{\[ōꂽ^pN̖30́CATPase[^[łSecAɂ쓮CSec߃^pNāCقǂꂽԂōזE𓧉߂C邢́C^pN͍זEɖߍ܂D
@M҂́C^pN̖߃`lł10񖌊ђʃ^pNSecYÊ̌\CٓIȍR̂Ƃ̂̂̕3.2𕪉\Ō肵<a href="#R31"><sup>31)</sup></a>i<a href="#F13">}13</a>jDSecYÊ͐^jłSec61̂ƂĕۑĂD܂ŕ񍐂ĂÍ׋ۂSecYÊ\ł̂ɑ΂<a href="#R32"><sup>32)</sup></a>C̍\͖ђʂփbNX݂ɊJđâւ݂`J\łD̑âւ݂ɂ͗A^pNN[̃VOiz񂪌C^pN̗AUN邱ƂꂽDVXeCˋ@pwIȉ͂ƌ\́Cq͊wV~[VɂCR̂ȂԂłSecYÊ͕\ƂĂCSecAi邢́C͕킵Ŕjƕ\J\ւƍ\ω邱Ƃ炩ɂꂽDɁCSecASecYÊƂVXeCˋ@pĉ͂ʁCSecASecYÊƌƊJ\ƂȂCATPase̘i邱Ƃ炩ɂꂽDȂ킿CSecASecYÊPƂł͕\ƂĂ邪C݂ɕ̂`邱ƂɂJ\ւƕωC^pN̖߂ЂNƂ炩ɂȂDSecASecYEĜ̒̕ᕪ\\<a href="#R33"><sup>33)</sup></a>ĈƂxĂD

<a name="F13"></a><div id="fig13-caption-text" style="display: none;"><strong>}13@SecYÊ̌\</strong>
[PDB IDF<a href="http://service.pdbj.org/mine/Detail2?PDBID=2zjs&PAGEID=Summary" target="_blank">2ZJS</a>]
<a href="http://leading.lifesciencedb.jp/wordpress/wp-content/uploads/2013/09/Nureki-2.e009-Fig.13.jpg" target="_blank">[Download]</a></div>[hs_figure id=13&amp;image=/wordpress/wp-content/uploads/2013/09/Nureki-2.e009-Fig.13.png&amp;caption=fig13-caption-text]

@ɍŋ߁CSecYÊƋ12񖌊ђʃ^pNSecDF̂ɂĂC\3.3𕪉\ŉ𖾂<a href="#R34"><sup>34)</sup></a>i<a href="http://first.lifesciencedb.jp/archives/2915" target="_blank">V_r[</a> łfځji<a href="#F14">}14</a>jDwIȉ͂ɂSecDF̂́CSecAϐ^pNSecYÊɉ񂾂̂C^pN̖߂ɂ̉ߒCH<sup>+</sup>̔Zxz̃GlM[pđi@\Ƃ炩ɂꂽ<a href="#R34"><sup>34)</sup></a>DɁCVXeCˋ@p͂ɂCSecDF̃yvYhC12̍\_Ci~bNɉ邱ƂɂCזE̊OւƗAĂ^pNSecYÊ肾ǂƂ𖾂炩ɂ<a href="#R34"><sup>34)</sup></a>DɁCdCwIȉ͂ƌu͂ɂCSecDF̂H<sup>+</sup>AVKH<sup>+</sup>`lłC쓮͂ƂăyvYhC1\ωԂƂɂC^pN̖A𑣐i閌VyƂĂ͂炭Ƃ؂CɁCH<sup>+</sup>̗Aɂ͂炭דdA~m_c𓯒肷邱Ƃɂ<a href="#R34"><sup>34)</sup></a>D

<a name="F14"></a><div id="fig14-caption-text" style="display: none;"><strong>}14@SecDF̂̌\</strong>
P1FyvYhC1D
[PDB IDF<a href="http://service.pdbj.org/mine/Detail2?PDBID=3aqp&PAGEID=Summary" target="_blank">3AQP</a>]
<a href="http://leading.lifesciencedb.jp/wordpress/wp-content/uploads/2013/09/Nureki-2.e009-Fig.14.jpg" target="_blank">[Download]</a></div>[hs_figure id=14&amp;image=/wordpress/wp-content/uploads/2013/09/Nureki-2.e009-Fig.14.png&amp;caption=fig14-caption-text]


<h2></h2>
@܂ŏqׂĂA^pN̍\wȌCA^pN͓Ǝ̊|PbgɂAFCAꎩ̂̂w|eVGlM[C邢́Cق̃CI̔ZxzATP̉̃GlM[pāCA쓮Ă邱Ƃ炩ɂȂDƂɁCCǏ⃊_Ȃǂɂ蓧ߍE̓̓d׏Ԃω邱ƂŁCAƂ̌𗣁C\ωUN邱ƂɂCA쓮Ƃq@\𖾂ꂽDɁCA^pN̑́CזEhCZT[ƂĂ͂炫AƑݍp邱Ƃł̏𖌊ђʃhCւƓ`BߍEJQ[eBO@\킹邱ƂɂCA𐧌䂷Ƃq@\𖾂D

<h2> </h2>
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</ol>
<div class="au-profile">
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<span class="author">G  iOsamu Nurekij</span>
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