̍\炩ɂG^pNê̎hê

<strong>V썄uEAG</strong>
iÉww@nȊw \q򗝊wj
emailF<a href="mailto:hiroaki.hidekazu@f.mbox.nagoya-u.ac.jp">AG</a>
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̈Zr[, <strong>2</strong>, e003 (2013)@<a href="http://dx.doi.org/10.7875/leading.author.2.e003">DOI: 10.7875/leading.author.2.e003</a>
Takeshi Tenno & Hidekazu Hiroaki: <strong>A common mechanism of signal transduction of G-protein-coupled receptors revealed by their three-dimensional structures.</strong>

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<h2>v </h2>
@2012Ñm[xw܂́CG^pNéiGPCRjɊւ錤ɂāCčDukewLefkowitzƕčStanfordwKobilkaɎ^ꂽDGPCR͍זE̊O̎hɓ`heƃVOi`B̌ƂȂ^pNłCn̕WIƂĂ߂ďdvłDCזEÕVOi𗧑̍\̕ωזEɓ`BƂ@\IȕKR̂߁CђʂփbNX̔zȂтɍזE[v̎ӂɂāC̗̍\̂ł̍\̂炬݂ĂC̍\͂͗eՂł͂ȂDזE[vT4]`[̂悤ȉñ^pNZ邱ƂɂC\ł̃<sub>2</sub>Ahiê̍\͂͂ȂꂽC̍\͂ɂ܂łɁC܂܂Ȍ҂ɂ葽GPCRɕՓIɉp̉\ȕ@_mꂽDƂ΁CL[rbNtF[Y@C邢́CM萫_ψّ̂OꊈpGPCR̃RA\̕tԂs^܂͊^̂ꂩɂ点Œ肷Ƃ@łD̕@͒PȂ\wɂZpJɂƂǂ܂炸CGPCR̃VOi`B@\̖{̗ɂ܂̂łDł́CGPCRɂVOi`B̕q@\ɂāCGPCR̗̍\͂̋ZpJ̐iWƊ֘AÂĉD

<h2>͂߂</h2>
@×CłƖ͕\̂łD邢́Ci̔ƊJ̗j́C̏ɂāCŕ̔Ƃ̗p̗jłƂĂߌł͂ȂDlނ͂̑āC܂łɑ̓łƏoC̈ꕔ̗LpɐĂDjIȌo܂̂ȂŎpĂȋ́Cl̂̃zIX^VX_o`B𐧌䂷G^pNéiG-protein coupled receptorFGPCRjWIƂ̂łD2012Ñm[xw܂́CčDukewRobert J. LefkowitzƕčStanfordwBrian K. KobilkáCGPCR̍\Ƌ@\Ɋւ钷Ňʂɑ΂^ꂽDƂŁCsvcȘbł͂邪CGPCR͕qw邢͍זEẘϓ_璍ړx̍^pNł͂ȂDƂ΁CȊwn̑w@ɂčLgpĂ鋳ȏwEssentialזEw 3<a href="#R1"><sup>1)</sup></a>xɂĂC킸\y[WĂɂȂDŁC̖򗝊wIȏdvCw␶w邢͖ẘ֌W҂́CmlmdvȕWI^pNƖڂĂD܂C\w҂͍\͂̍ȃ^pN̑\iƂĂD̃m[xw܂ɂȂƐт́C̋@\͂zIX^VX_o`BȂǂ߂ďdvȐۂɋʂȋ@\̉𖾂ɂāC̒[JƂ_ŔɈӋ`[D

<h2>1DGPCR̕</h2>
@܂CA~m_ꎟzɂƂÂGPCR̕ނƁCꂼ̊{IȐ@\ɂĕKĂDGPCR̓yv`hzᕪqKhC邢́CȂǂ̍זEÕVOieCזEɓ`̂傽@\łDGPCR̎v3̃NXɂĂi<a href="#F1">}1</a>jD̕ނ́CI_CMBIiCentre for Molecular and Biomolecular InformaticsǰJĂf[^x[XGPCRDB <a href="#R2"><sup>2,3)</sup></a>iURLF<a href="http://www.GPCR.org/7tm/" target="_blank">http://www.GPCR.org/7tm/</a>jQlɂĂD_ŁCqg̃Qmɂ͂悻1400GPCR̈`q݂ĂC̐͑S`q̂悻5ɂyԁD̂CƂ͚̂koêłDGPCŔCS̃A~m_z̑ɂƂÂ5̃NXɕނĂD

<a name="F1"></a><div id="fig1-caption-text" style="display: none;"><strong>}1@GPCR̕ނƂꂼ̃NX̓</strong>
NXAN[ȂтC[ɂ郋[vZC܂́Cɂق̍\hCȂDNXBN[ɂ100`300c̃yv`hzhCCNXCN[ɂ300`600c̃KhhC݂D܂CNXC͍זEɂC[[vD7{̖ђʃwbNX͂悻25`35cȂC̖ђʃwbNXA郋[v́CזEO[viECL1`ECL3jCсCזE[viICL1`ICL3jƖOĂD
<a href="http://leading.lifesciencedb.jp/wordpress/wp-content/uploads/2013/03/Hiroaki-2.e003-Fig.1.jpg" target="_blank">[Download]</a></div>[hs_figure id=1&amp;image=/wordpress/wp-content/uploads/2013/03/Hiroaki-2.e003-Fig.1.png&amp;caption=fig1-caption-text]

@łɂƂ肠NXAihvVt@~[Ƃ΂j́CN[ȂтC[ɂ郋[vZC܂́Cɂق̍\hCȂ^CvłDJeR[A~⎉n̒ᕪqKhi̐_o`B܂ށjCyv`hziGhZȂǁjeăVOi`BsDŏɍ\͂ꂽhvV́C̃Kh̑Ɍeqł郌`i[Lɂ茋ĂDNXAɂ́CokoȂǂ̊oC_o`BCzIX^VẌێȂǁC߂ďdvȐ@\ɂGPCR܂܂ĂD
@ł͊邪Cn̕WIƂĒڂĂJeS[ƂāCNXBiZN`ẽt@~[Ƃ΂jƁCNXCiӌ^O^~_ẽt@~[Ƃ΂jDNXB́CN[100`300A~m_cƂⒷ̈Cɖ100A~m_c̃yv`hzhCi܂́CPɍזEOhCƂ΂j݂CZN`ȂǃWXtBh܂܂Ȃyv`hz̎h`BsDNXĆCN[ɖ300A~m_cƂɒ̈CɃA~m_Ȃǂɑ΂郊KhhC݂DNXC̑\͐_o`BɌȂO^~_êłD낢ƂɁCNXĈKhhC͐^׋ۂɂĂ`IɕۑĂCyvYɂăA~m_IAȂǂɋ@\^pN̂hCƗ̍\߂ėގĂD
@̂قɁCWntVOi`BnɂăVOie7񖌊ђʌ^eFrizzledCŷڍqêȂǂCꂼCɏqׂ̂Ƃ͕ʂGPCR̃t@~[Ƃĕނ邱Ƃ邪Cs̃f[^x[XGPCRDBɂ͎ڂĂȂD

<h2>2DGPCRɂVOi`B̂</h2>
@GPCRɃKhGPCR̖ђʂփbNX̗̍\ɕωNC̕ωזE[vɓ`āCʓIɁCזE[vɌweOʑ̌^GTP^pNɓ`B<a href="#R4"><sup>4)</sup></a>D̃weOʑ̌^GTP^pNiȉCPG^pNƂԁj́Ĉ̖ƂCCC3̃TujbgȂ^pNłĈGTPƌ̂̓TujbgłDG^pNɂ͕̎ނC̎ނɂזEɓ`VOi͑傫قȂDƂΚMނɂāCTujbgCTujbgCTujbg̕q́CꂼC20ށC6ށC12ނ݂ĂDGPCRłɋG^pN̎ނقȂΐIɊƗ}̐΂̔ЂNƂĈƂGPCRɊ֌W鐶ۂ̕Ǧ̂ЂƂƂȂĂDG^pNɂĂCזEBɂVOi`BȂǂŒmᕪqG^pNȂǂƓlɁCGDP^s^CGTP^^łDKhGPCRɌ邱ƂɂVOiG^pÑTujbgɓ`BDƁC܂ŕs^łG^pNGDPGTPɌCTujbgƃTujbg2ɉ𗣂DTujbgƃTujbg͂ꂼGPCR𗣂Cʌ̃GtFN^[qɍpăVOi`BĂi<a href="#F2">}2</a>jD

<a name="F2"></a><div id="fig2-caption-text" style="display: none;"><strong>}2@G^pNɂVOi`B@\Ƃ̗̍\</strong>
iajG^pNɂVOi`B@\DGDP^s^CGTP^^DKhGPCRɌGDPGTPɕϊCTujbgƃTujbgꂼGPCR𗣂Cʌ̃GtFN^[qɍpăVOi`BĂD
ibjGDP^G^pŇ\iPDB IDF<a href="http://service.pdbj.org/mine/Detail2?PDBID=3ah8&PAGEID=Summary" target="_blank">3AH8</a>jDΐFFTujbgCFFTujbgCsNFFTujbgCIWFFGDPD̍\G<sub>q</sub>^pNƑjQ܂̂̂̕ŉꂽ̂Cł͑jQ܂͏ȂĂD
<a href="http://leading.lifesciencedb.jp/wordpress/wp-content/uploads/2013/03/Hiroaki-2.e003-Fig.2.jpg" target="_blank">[Download]</a></div>[hs_figure id=2&amp;image=/wordpress/wp-content/uploads/2013/03/Hiroaki-2.e003-Fig.2.png&amp;caption=fig2-caption-text]

@GPCR̎ނȂтɂꂪĂזEɂCGPCRƋĂG^pN̎ނقȂĂD̓Tujbg̔zɂCG<sub>s</sub>CG<sub>i/o</sub>CG<sub>q</sub>CG<sub>12/13</sub>4̃^CvɑʂDG<sub>s</sub>s͊istimulationj̓ӖCyfłAfj_VN[[邱Ƃɂ㑱VOi`BJXP[h̏sD܂CzXzp[[A2邢̓zXzp[[CȂǂčזEɃVOi`BDꂽAfj_VN[[ɂ萶ꂽcAMṔCveCLi[[AčL͂ȍזEhǂZJhbZW[łDCG<sub>i/o</sub>i/o͑jQiinhibitoryj/̑iotherj̓ӖC΂΃Afj_VN[[̊jQ邽߁CG<sub>s</sub>ɗRVOi̗}SD̂قCTujbgăzXt@`WCmVg[ٓIzXzp[[CzXzWGXe[[ȂǁCL͂ȃVOi`BnɊ֗^ĂD2̎vȃ^Cv̂قCzXzp[[CG<sub>q</sub>CᕪqG^pNłRasRhoVOi`BnƃNXg[NG<sub>12/13</sub>D

<h2>3DGPCRɓIȖ򗝍p</h2>
@GPCRɂ̓zê_o`BêȂǂ܂܂D̂߁Cʏ̍yfjQ܂`lubJ[Ƃ͈قȂCGPCRɍp򕨂͖򗝊wIɂ2ނɑʂDȂ킿CASjXgi쓮jƃA^SjXgihRjłDASjXg͂̎ê̐IȃKhƓl̐pЂN򕨂łCA^SjXg͐IȃKh̍pɝhRĂjQ򕨂łDʏC򕨂̍px͖򕨂ƕWIƂȂêƂ̉𗣒萔i<em>K</em><sub>d</sub>jɂӓIɒ߂ׂ̂ł邪CGPCR̃ASjXgɂ͑ߏ𓊗^Ă{̐IȃKhN鐶̕IȊȂ̂DŁC𗣒萔Ƃ͕ʂɁCOaƂ100̐ЂN̂SASjXgCȂƂȂ̂𕔕ASjXgƂŋʂĂD܂CȂȂGPCR̓KȟĂȂԂłx̃VOi`BsĂD́C΁CԂ̃GW̃AChO]ɑ銈ŁCbi܂́CԊjƂԁDʏ̃A^SjXg͎êɂVOi`B̊͑jQ̂́C̊bɂ͉eȂDCCo[XASjXgit쓮jƂ΂򕨂́C̊bɗ}򕨂łDGPCR̊֗^nł͂畡GȌۂÂmĂC̕q@\̉𖾂҂ĂD

<h2>4DGPCŘ̂ӂFêƃKh</h2>
@Kobilka̋Ɛтɂ킦C܂GPCR̍\ł̗̍\͂ɐZpmɍvCStevensičScripps Research InstitutejCTateipMRC Laboratory of Molecular BiologyjCсC킪̊c zisww@wȁjɂ鐬ʂɂďЉDȂCGPCŘ@̐iWɂāCMɎW54PDBGg[ɂ錋̏Ȃǂ܂Ƃ߂̂Supplementary TableƂēYti<a href="#F6">\1</a>jDꂪǎ҂̈ꏕɂȂ΂ƊĂD

<a name="F6"></a><strong>\1@GPCR@̐iW</strong>
2013N110 
<a href="http://leading.lifesciencedb.jp/wordpress/wp-content/uploads/2013/03/Hiroaki-2.e003-Suppl.xls" target="_blank">[Download]</a>

@GPCR͏dvȑn^[QbgłƂC̍\ɂނđ̓w͂ȂĂD\ɂĂ͂ǂ́C1jĝGPCRʂɓȂƁC2jȂCƂꂽƂĂC\̈ƁCłD̕ǂ̓^pŇɂĂ˂ɂ͂̂ł邪CGPCRɂĂ͂ƂɍǂłD
@gGPCR𓾂@ƂāC咰ۂ^jזE܂ŁC܂܂ȕ@ĂDM҂炪ׂC܂łɗ̍\񍐂ꂽGPCR̂قƂǂ͍זE璲ĂCقɂ́C^m[yi<em>Pichia pastris</em>j3C咰ہiőNMRɂ͂sꂽj1łDāCɓK𓾂邽߁CђʂփbNXւ̕ψق̓ɂ艻<a href="#R5"><sup>5,6)</sup></a>CN[C[C邢́CזE[vȂǂ̐؏<a href="#R7"><sup>7)</sup></a>CɂCAXpMcق̎cւ̕ψفCȂǂsꂽD̉ς̓Khɑ΂ea⊈\ɉe\邽߁C쐶^ƔrŌɓKRXgNgIꂽD
@GPCR͍זEɖߍ܂Ă̂ŁCזEjӂĒSƕsn敪ɑ݂D̕sn敪GPCR𓾂ɂ͊Eʊ܂ɂGPCRnKv邪C̈ŁCEʊ܂̎gpGPCRϐĂ܂\DāCEʊ܂̎ނʂ̏GPCR̍\͂ɂďdvłD\̕񍐂ĂGPCRł́Cn<em>n</em>-hfV--D-}gVhiDDMjƂgĂC30ႠDDDM͐e̕}g[XƂȂĂCIEʊ܂łCGPCRɂ炸ق̖^pN̍\͂ɂ悭gĂD܂C22ɂẮC̓rɊEʊ܂Cɂĕʂ̊Eʊ܂gpĂDɁCVEʊ܂̓i߂ĂC7ɂāC2{̃}g[X2{̒Yf}g[XlIy`OR[iMNGjpĂ<a href="#R8"><sup>8)</sup></a>DMNG̓~Ž`ՊE~ZZxDDM1ĈƂGPCR̈艻Ɋ^̂ȂD
@GPCR̓KhƂ̌ɂ肻̃Rz[Vω邱ƂōזEG^pN̊ЂNDcȐwIі򗝊wIȌCGPCR̂Ȃɂ̓KhƌĂȂĂ̊\̂C̃KhƂ̌\KhƂɊ\̈قȂ݂̂DO҂́CKhƌĂȂԂɂĊ^ƕs^Ƃ̓It݂邱ƁC҂́C郊KhɂRz[VὠxقȂ邱ƂĂCCGPCR̃VOi`B@\ɓIȃRz[Vω̉ߒ݂Ă邱ƂĂDCGPCR̓IȐ͌邤ł͕ssƂȂ邽߁CGPCR̐̂Ƃ烊Kh킦CψȃRz[VƂȂ悤Ă邱ƂDpĂ郊Khɂ́CSȊԂɗU銮SASjXgCアԂŌŒ肷镔ASjXgCsԂɌŒ肷A^SjXg̓Co[XASjXgDCo[XASjXg̓KhƌĂȂԂł\<sub>2</sub>Ahiê̍\͂ɂėpCϋɓIɕsԂɌŒ肷邱Ƃɂ\͂𐬌ɓ<a href="#R9"><sup>9,10)</sup></a>D
@̒ɂẮCقɂGPCRɕۂ߂̏CȂǁC܂܂ȂӂȂĂC̎͂قƂǂ̘_ɂĖ{ł͂ȂICɂSupplementary InformationɍׂLqĂDSupplementary Information͍\͂ɂ`[̔S苭w͂̌łCЈǂ߂D

<h2>5DGPCŘ̂ӂF̍쐻</h2>
@̒ɂ邭ӂɂψȃRz[VƂ肤鎎𓾂邱Ƃ\ƂȂƂĂCcOȂC܂\͂ɑ镪\͓ȂDȂȂCGPCRɂ͉^̍זE[v݂قC~ZɂꂽGPCR͊iqɂ͐񂵂ɂłD
@2007NC2ނ̃<sub>2</sub>Ahiê̗̍\񍐂ꂽD́CזE[vƓٓIɑݍpŔiFabtOgj쐻ċɂ蓾ꂽ\ĆCזE[v̈ꕔt@[WɗRT4]`[ƒuč쐻L^pŇɂ蓾ꂽ\ł<a href="#R9"><sup>9,10)</sup></a>D܂܂ȐwIȌɂC7{̖ђʃwbNX̂C5ԖځiTM5j6ԖځiTM6jȂ3Ԗڂ̍זE[viICL3j͔ɍ^ƂĂD̉^}邽߁CCo[XASjXgƂ̌ɂsԂ̃Rz[VƂ<sub>2</sub>Ahiê̎ƂɁCICL3F郂mN[iR̂쐻ꂽ<a href="#R11"><sup>11)</sup></a>DʓIɂ́CR̂ƌ<sub>2</sub>AhiễKhƂ̌\͍R̂ȂƂƂقƂǕςȂICL3̉^͗}ĂȂCR̂ɂë̗̊g債ƂɊ^̂ƎvꂽDCICL3T4]`[ɂuL^pN̍\͂ł́Cłɍ\̕񍐂ĂhvVTM5TM6Ƃ̋ƁCT4]`[N[C[Ƃ̋ɒڂCICL3ւT4]`[̑}ӏ̈قȂ镡̔RXgNg쐻ꂽDāCKhƂ̌AbZCƂɌɗp鎎IʂCɁĈɏqׂ鎉L[rbNtF[Y@𓱓邱Ƃɂ茋ɐ<a href="#R12"><sup>12)</sup></a>D
@2011NC<sub>2</sub>AhiêT4]`[Ƃ̃L^pNɂāCזËɌim{fBp\񍐂ꂽ<a href="#R13"><sup>13)</sup></a>Dim{fB̓N_ɗRR̂łCd݂̂\15 kDaƔrID̍R̂͂̏łȂCPhCȂ邽ߑ咰ۂył\łƂbg<a href="#R14"><sup>14)</sup></a>D̃im{fB̌́CASjXgƌԂ̃<sub>2</sub>Ahiê̈艻Ɋ^Č𐬌ɓDCT4]`[Ƃ̃L^pNƂ@́CICL3łȂCN[ɗZꍇɂɐD܂CL^pNp[gi[ƂĔM艻A|VgN<em>b</em><sub>562</sub>RIL<a href="#R15"><sup>15)</sup></a>C2012NCN[ɗZN/QFQIsIChéCсCICL3ɑ}A<sub>2A</sub>AfmVê̍\͂񍐂ꂽD
@GPCŘɂẮCɏqׂ悤ɁCL[rbNtF[Y@i\tF[Y@Ƃ΂j<sub>2</sub>AhiêT4]`[Ƃ̃L^pN̍\͂ɂĂ͂߂ėpĈ̂CGPCR̍\̖͂񔼐ɂėpĂD̕@́Cntɂ郂mICiOZ[1q̃IC_GXej̔䗦Ɖx̕ωɂN鑊]ڂ𗘗pDGPCR̎ƃmICCRXe[̍ɒa܂킦ƁC]ڂɂẘiq\ƂȂD̂ƂCdɂł͂킦RXe[ɂ͂GPCR񂵂ĂDCdƒs鐂ł́Cd̗ɓ˂oGPCR̍זEÖƍזËɂe̕Ƃݍpđwd˂ĂDGPCRT4]`[R̂ȂǂĂƂɂ́C̕ƂȂďdwĂ̂ƍlĂ<a href="#R16"><sup>16)</sup></a>D<sub>2</sub>Ahiê̍\͂̌ʂCTM2TM4ɕۑꂽRXe[`[t݂̑ꂽ<a href="#R17"><sup>17)</sup></a>D̂悤ɎL[rbNtF[Y@ɂGPCRK񂷂邱ƂŁC荂\̍\͂Bł̂낤DCV``Ẽ<sub>1</sub>Ahiê̍\͂ɂẮCN[C[̐؏CɁCψق̓ɂ芈ȃ<sub>1</sub>Ahiê<a href="#R6"><sup>6)</sup></a>CCgU@ɂ錋ɐD

<h2>6DNXAGPCR̔r</h2>
@NXAGPCR̓hvVt@~[ƂChvVɑ΂A~m_z̕ۑrID̂Ƃ́Cɏqׂ悤ɁC2007Nɕ񍐂ꂽ<sub>2</sub>AhiêT4]`[Ƃ̃L^pN̍\́CT4]`[ƃhvṼf[^Ƃɕqu@ɂ茈肳ꂽƂ炩ł낤D
@7{̖ђʃwbNXiTM1`TM7j̔zu͂ǂGPCRłłCזEGPCR̍זE݂ƂCђʃwbNX͎vɔzuĂDCђʃwbNX̑ΓIȈʒupxCɂĂGPCRɂႢi<a href="#F3">}3a</a>jDƂ΁CEṼhvV̍\iPDB IDF<a href="http://service.pdbj.org/mine/Detail2?PDBID=1u39&PAGEID=Summary" target="_blank">1U39</a>jƂƁCXtBSKhƂS1P<sub>1</sub>éiPDB IDF<a href="http://service.pdbj.org/mine/Detail2?PDBID=3v2w&PAGEID=Summary" target="_blank">3V2W</a>jTM1TM2TM3ւނċ߂ÂĂD疌ђʃwbNẌʒüႢS1P<sub>1</sub>êTM1TM7Ƃ̂ɂ͌ԂCXtBŠԂʉ߂S1P<sub>1</sub>ê̓̃|PbgɃANZXĂ\ꂽD

<a name="F3"></a><div id="fig3-caption-text" style="display: none;"><strong>}3@NXAGPCR̍\̔r</strong>
iaj<sub>2</sub>Ahiê̍זË̗iPDB IDF<a href="http://service.pdbj.org/mine/Detail2?PDBID=2rh1&PAGEID=Summary" target="_blank">2RH1</a>jD
ibj<sub>2</sub>Ahiêɂĕs^Ɗ^Ƃ̏dˍ킹Ds^͎FCPDB IDF<a href="http://service.pdbj.org/mine/Detail2?PDBID=2rh1&PAGEID=Summary" target="_blank">2RH1</a>CCo[XASjXg̓J][D^͐FCPDB IDF<a href="http://service.pdbj.org/mine/Detail2?PDBID=3p0g&PAGEID=Summary" target="_blank">3P0G</a>CASjXgBI-167107D
icjA<sub>2A</sub>AfmVêɂĕs^Ɗ^Ƃ̏dˍ킹Ds^͉ΐFCPDB IDF<a href="http://service.pdbj.org/mine/Detail2?PDBID=3pwh&PAGEID=Summary" target="_blank">3PWH</a>CCo[XASjXgZM241385D^͒FCPDB IDF<a href="http://service.pdbj.org/mine/Detail2?PDBID=3qak&PAGEID=Summary" target="_blank">3QAK</a>CASjXgUK-432907D
idjqX^~H1êCXCR4PJCêƂ̏dˍ킹DqX^~H1ê͒FCPDB IDF<a href="http://service.pdbj.org/mine/Detail2?PDBID=3rze&PAGEID=Summary" target="_blank">3RZE</a>CA^SjXg̓hLZsDCXCR4PJCê͐FCPDB IDF<a href="http://service.pdbj.org/mine/Detail2?PDBID=3odu&PAGEID=Summary" target="_blank">3ODU</a>CA^SjXgIt1tD
iejA<sub>2A</sub>AfmVêɂĊ^ƕs^Ƃ̏dˍ킹D^͒FCPDB IDF<a href="http://service.pdbj.org/mine/Detail2?PDBID=3qak&PAGEID=Summary" target="_blank">3QAK</a>CASjXgUK-432907Ds^͐FCPDB IDF<a href="http://service.pdbj.org/mine/Detail2?PDBID=3pwh&PAGEID=Summary" target="_blank">3PWH</a>CCo[XASjXgZM241385D
<a href="http://leading.lifesciencedb.jp/wordpress/wp-content/uploads/2013/03/Hiroaki-2.e003-Fig.3.jpg" target="_blank">[Download]</a></div>[hs_figure id=3&amp;image=/wordpress/wp-content/uploads/2013/03/Hiroaki-2.e003-Fig.3.png&amp;caption=fig3-caption-text]

@܂CGPCRłĂ郊KhςƖђʃwbNẌʒuƊpxωĂC̕ωזEÕVOiזE֓`镪q@\̌łD܂łɁCASjXǧ^ƁCA^SjXg̓Co[XASjXǧs^̗̍\肳Ă̂́C<sub>2</sub>AhiéC<sub>1</sub>AhiéCA<sub>2A</sub>AfmVêłD^ƕs^GPCR̈ႢזE݂ƁC<sub>2</sub>Ahiêł́CTM5͒SOւ̈ړCTM6͎v̉]ƊOւ̈ړCTM3TM7͓ւ̈ړĂi<a href="#F3">}3b</a>jDCA<sub>2A</sub>AfmVêł́CTM3͍זEOւނĂ̈ړCTM5TM6ւނĂ̈ړCTM6͎v̉]ƊOւ̈ړCTM7͓ւ̈ړĂi<a href="#F3">}3c</a>jD̃Rz[V̕ωɂ͌̏Ȃǂɂe̊܂܂Ă\邪CASjXǧɂ錋|Pbg̎ӂ̏ȕωђʃwbNẌړ]UNCGPCR̍זEɑ傫ȕω𐶂ĂD
@זEÖ̗N[̈3̍זEO[viECL1`ECL3j\Ă邪C̃A~m_zGPCR̂ł܂ۑĂ炸CقȂDזEO[v͒PɖђʃwbNXȂł邾ł͂ȂCṼKh}ƂȂCGPCRɂĂ̓KhƂ̌Ɋ^ĂꍇD<sub>1</sub>AhiéC<sub>2</sub>AhiéCS1P<sub>1</sub>XtBSêɂẮCECL2ɃwbNX݂DCCXCR4PJCéCj[eVéCPAR1veA[[éCIsIChéCȃIsIChéCʃIsIChéCmVZv`êɂẮCECL2ɃV[g`ĂCA<sub>2A</sub>AfmVêɂẮCECL1ECL2Ƃ̂ɃV[g`ĂDECL2TM3̍זEÔɂ̓WXtBh`ĂCECL2̂炬}ĂD̃WXtBh̓NXAGPCR̂ŕۑĂ邪CS1P<sub>1</sub>XtBSêɂĂTM3̍זEOɃVXeCcȂ̂ł݂͑ȂDhvVɂāCזEɂC[ɂ8{ڂ̃wbNX݂邪C͂ق̃NXAGPCRɂĂ݂邱ƂD
@KȟʒuGPCR̂ŏقȂĂDђʗ̈̐[ʒuŌĂ̂́ChvVi11-<em>cis</em>-`i[jCXJM2éi3-LkNWjxW[gjCXJM3éi`IgsEjCqX^~H1éihLZsjłDtɁCrI󂢈ʒuŌĂ̂́Ch[p~D3éiG`NvhjCCXCR4PJCéiIt1tjCS1P<sub>1</sub>XtBSéiXtBS͕퉻jCj[eVêłi<a href="#F3">}3d</a>jD܂CGPCRłKhɂ茋镔ʂ͈قȂĂCƂA<sub>2A</sub>AfmVê̏ꍇCASjXgUK-432097͖ђʗ̈̐[ʒu܂œ荞ŌĂCCo[XASjXgZM241385͐󂢈ʒuŌĂi<a href="#F3">}3e</a>jD

<h2>7DGPCRɂ郊Kh̔F@\Fj[eVêƂ</h2>
@ۂ̍\̗͂QlɂȂGPCRɂ郊Kh̔F@\ƃVOi`B@\DƂ肠̂́C܂ŏЉĂȂGPCR̉͂ɐЂƂ̌łGrisshammeričNIHjɂ鐬ʂŁC2012Nɕ񍐂ꂽCj[eVêƃj[eVi̕yv`hjƂ̂̍̕\ł<a href="#R17"><sup>17)</sup></a>Dj[eV̓EV̎Ŕꂽ13A~m_cȂyv`hzłCǂ̊gƌ̍~pCǂ̎kpCÍpȂǂmD܂łɑ̃ASjXg邢̓A^SjXgGPCRƂ̂̍̕\񍐂Ă邪Cyv`hzƌĂ̂ƂẮC̍\͂߂Ăł̂ŗƂđI񂾁Dɂ́Cj[eVê3Ԗڂ̍זE[vT4]`[ɂuL^pNpꂽD̓oLECX-זEnpĔ̂CEʊ܂ƂĂMNGgpꂽDŏIIɁCL[rbNtF[Y@ɂ茋C2.8𕪉\ŉ͂ꂽ<a href="#R18"><sup>18)</sup></a>D
@ꂽ̍\̓܂Ƃ߂ƁCȉ̓_ɏW񂳂D1jꂽj[eVê̗̍\hvVCсC<sub>2</sub>Ahiê̊^ѕs^̍\ƔrƁC^̃<sub>2</sub>Ahiê̍\ɗގĂD2jꂽ̍\זE݂ƁCђʂփbNXiTMj̑ΔzuɂāCTM5TM6̂ɊĂCɁCTM6אڂĂTM3痣TM5̂قɊzuƂȂĂi<a href="#F4">}4a</a>jDj[eVêɂ郊Khʂ́C1Ԗڂ6{̖ђʃwbNXTM2`TM7̍זEO̎cƁCN[[v3{̍זEO[vECL1`ECL3ɂ\ꂽ[L|PbgłCƂECL2ECL3CTM6TM7ɗRcƑ̑ݍp݂ꂽDKhƃj[eVễA~m_cƂ̂̂ȑݍṕCfѐÓdIݍpłD

<a name="F4"></a><div id="fig4-caption-text" style="display: none;"><strong>}4@j[eVê̊̋@\ƃKhƂ̌</strong>
iajj[eVêƃj[eVƂ̂̕ɂ閌ђʃwbNXiTMj̔zuCs^ъ^̃hvV̗̍\Ədˍ킹ĔrDdˍ킹ɂTM1`TM4TM7pCTM5TM6̑Δzu̕ω킩₷Ȃ悤DDFFs^̃hvViPDB IDF<a href="http://service.pdbj.org/mine/Detail2?PDBID=1gzm&PAGEID=Summary" target="_blank">1GZM</a>jCFF^̃hvViPDB IDF<a href="http://service.pdbj.org/mine/Detail2?PDBID=3pqr&PAGEID=Summary" target="_blank">3PQR</a>jCFFj[eVe-j[eV́iPDB IDF<a href="http://service.pdbj.org/mine/Detail2?PDBID=4grv&PAGEID=Summary" target="_blank">4GRV</a>jDhvVł͎ê̊ɂƂȂCTM5TM6̈ʒu傫ړĂ邱Ƃ킩D
ibjj[eVêƃj[eVƂ̂̍̕\Dłɖ炩ɂĂGPCR̃Khʂ̂悻̈ʒuDNTS<sub>8-13</sub>Fj[eVyv`hi8`13cjD
<a href="http://leading.lifesciencedb.jp/wordpress/wp-content/uploads/2013/03/Hiroaki-2.e003-Fig.4.jpg" target="_blank">[Download]</a></div>[hs_figure id=4&amp;image=/wordpress/wp-content/uploads/2013/03/Hiroaki-2.e003-Fig.4.png&amp;caption=fig4-caption-text]

@̍\͂ł̓KhƌĂȂԂ̃j[eVê̗̍\͖炩ɂĂȂ߁CKhƂ̌̑Ołǂ̂悤ȍ\ωN̂C̏ڍׂ͖młDCASjXgƂ̌ɂUNRz[V̕ωCȂ킿CTM5TM6ΔzuςCŏIIICL2ICL3̗̍\̕ωЂN_͋ʂłDCKhʂ́g[h̓_ł͑傫قȂĂDhvVɂݐKhłS<em>trans</em>`m[C<sub>1</sub>AhiễKhłC\viCA<sub>2A</sub>AfmVễKhłAfmVȂǂ́CђʃwbNX̂薌̒Sɋ߂[Ɍ邱Ƃō\ωNDɑ΂Cj[eV̌ʂ͂烊Kȟʂ5߂OiזE̊Ojɋ߂i󂢁jƂłi<a href="#F4">}4b</a>jDāCKhƂ̌ʂ͈قȂ̂ɐRz[Vω͋ʂł邱Ƃ́C^̃<sub>2</sub>AhiêA<sub>2A</sub>AfmVê̍\玦Ă̂Ƃ͈قȂ镪q@\ɂCj[eVê͊^̃Rz[VƂ邱ƂD

<h2>8DGPCRɂVOi`B@\FG^pNɂڂ\ω</h2>
@GPCRɂVOi̎eŏIIɂǂ̂悤G^pNɓ`B邩ɂĊȒPɏЉD̕q@\̉𖾂ɑ傫v̂́C2011ŃCASjXg^̃<sub>2</sub>AhiêƃkNI`h񌋍^G^pNƂ̂̍̕\͂̕񍐂ł<a href="#R19"><sup>19)</sup></a>i<a href="#F5">}5a</a>jDɏqׂ悤ɁCASjXgƂ̌ɂGPCRɂЂN闧̍\̕ώCזE̓ɂTM6̎v̉]ƂČĎʁCTM5TM6Ƃ̂ɍa`CGPCRG^pNƂ̂̕ɂẮCG^pÑTujbĝ5wbNXĂDCTM6ƃ5փbNXƂ̈ʒu֌W͂܂ŃhvVƃgXW[VɗRyv`hƂ̂̍̕\\Ă̂Ƃ͈قȂĂDȂ킿CGPCRƂ̑ݍpɂזEɂăTujbgRaslhC̃Rz[VωCÂāC̕ωɂƂȂTujbgɌIȍ\ωUƗ\ꂽDGPCRƂ̂̕oG^pN̗̍\i<a href="#F5">}5b</a>jCGDP^G^pN̗̍\i<a href="#F2">}2b</a>jƔrƂ킩悤ɁCGPCRƂ̂̓̕Tujbg̃wJhCƂ΂̈悪Ăiۂ́CȂȂ킯ł͂ȂChC̈ʒu֌Wpxɂ130x߂]^NC̐}̔wʂɂ܂肱łjDĂ̌ʁC܂GDP͂܂悤ɂČĂʂC傫n}ɘIoGDP̉𗣂悤ȍ\ƂȂĂD̂̂CᕪqG^pNɂVOi`B̃XL[ƓCGTP邱ƂŃTujbg̍\͊^ւƕωC̕qւƃVOi`BJXP[hJn̂ł낤D

<a name="F5"></a><div id="fig5-caption-text" style="display: none;"><strong>}5@GPCRɂVOi`B@\</strong>
iaj<sub>2</sub>AhiêG^pNƂ̂̌̕\iPDB IDF<a href="http://service.pdbj.org/mine/Detail2?PDBID=3sn6&PAGEID=Summary" target="_blank">3SN6</a>jDΐFFTujbgCFFTujbgCFFTujbgD<sub>2</sub>AhiéisNFjN[ɂT4]`[ZC܂CזEɂ͍RV <sub>HH</sub>tOgiΐFjĂD
ibj<sub>2</sub>AhiêG^pNƂ̂̌̕\G^pN݂̂oDkNI`hʂ͗n}ɘIoĂD
<a href="http://leading.lifesciencedb.jp/wordpress/wp-content/uploads/2013/03/Hiroaki-2.e003-Fig.5.jpg" target="_blank">[Download]</a></div>[hs_figure id=5&amp;image=/wordpress/wp-content/uploads/2013/03/Hiroaki-2.e003-Fig.5.png&amp;caption=fig5-caption-text]


<h2></h2>
@܂ŉ𖾂ĂȂê̗̍\ƃVOi`B̕q@\炩ɂ邱ƂɂCȊw̑̕iƂ΁CqwC^pNȊwCnCoCICtH}eBNXɂ킦CƂɂ́C_oȊw򗝊wȂǂ܂܂jɉeCȌ̌̒猈肵Ă܂ƂƂ肠DLefkowitzKobilkagȑOh̖򗝊w̌܂ɂłDKhזEgD邢͂̓^ʂɂ܂t̖򗝊CɁCêĈقȂ鐶ۂЂNƂׂƂ󋵂́CGPCRɊւ邩C򗝊wƂw𕡎GȈËLwƂC̈wіw̕s]𔃂ĂDM҂̐ł͂邪ĈȗŔCGPCRɍp鐶̓Kh򕨂̂炷ۂG\s\ŁCeՂɗ邢͐ł͂Ȃ낤H@ChvV̍\̌ɂ[؂<a href="#R20"><sup>20)</sup></a>Ĉ̂C}ɔW\@̊mƕyɂC킸ȊԂɑGPCRɂč\𖾂ȂCȕq򗝊w̎̓ꂽDGPCR̍\͂炵ƂɁĆCASjXgCASjXgCA^SjXgCA^SjXgCCo[XASjXgȂǁC܂ňȏɖLxȎނ̖򕨂̊JI_Iɐi߂ĂƂɂȂ낤Dɋ[Ƃ́CGPCR̃VOi`B@\̂̂ɓ݂铮Iȍ\̗CʓIɂ܂܂Ȏ@𐶂ݏo_@ƂȂC\̐炵ƂłDntNMR@⏬pU@ƈقȂC{͐ÓIȍ\Ȃ͂X͂oGPCR̍\ԂČ҂ɂZp̐ςݏd˂̗j΂C胊AȂ̂ƂĂ܂Ă̂ł͂Ȃ낤D̗̍\̂̓It^pN̍\炬ƂgI\ĥ炷IȌۂ̏dv́CGPCR̂قɂCᕪqG^pNjê̊֗^VOi`BɂĔFm͂߂ĂC\wɂVȌTOƂȂDVTO̊mn̕Ƀp_CVtg炷߂ƍlD

<h2> </h2>
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</ol>
<div class="au-profile">
<h2>҃vtB[</h2>
<span class="author">V uiTakeshi Tennoj</span>
F2004N Qww@Hw CCN lsww@w C2005N sww@Hw C2007N _ˑww@wn C2011N Éww CoāC2012N薼Éww@nȊw D
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<strong>A GiHidekazu Hiroakij</strong>
F1992N w@wȔmے CCN {V C1996N qHwC2001N lsww@w C2007N _ˑww@wn C2011N Éww oāC2012N薼Éww@nȊw D
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URLF<a href="http://presat-vector.org/hiroaki-lab/" target="_blank">http://presat-vector.org/hiroaki-lab/</a>
</div>
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