瀹為獙瀹ゆ柊闂?/h4>
闄堥箯璇鹃缁勫彂鐜扮敳閱涒�滄縺娲烩�濊泲鐧借川鐨勭嫭鐗瑰寲瀛︿慨楗?/h1>
浣滆�咃細
鏉ユ簮锛?nbsp;
鍙戝竷鏃ユ湡:2021-01-29
浣滀负涓�绉?/span>鐢熸椿涓?/span>鐨勫父瑙?/span>鑷寸檶鐗╋紝鐢查啗浼?/span>瀵逛汉浣?/span>浜х敓寰堝ぇ鐨?/span>鍗卞銆備絾鍙︿竴鏂归潰锛岀敓鐗╀綋鏈韩涔?/span>浜х敓涓�瀹?/span>閲?/span>鐨勭敳閱涖�?/span>杩欎簺鈥滃唴婧愨�?/span>鐢查啗鍒嗗瓙鏄?/span>澶氭潯鐢熺悊浠ｈ阿閫斿緞鐨?/span>鍘熸枡鎴栦骇鐗?/span>锛?/span>涓?/span>缁嗚優鐨勫瓨娲讳笌鐢熼暱瀵嗗垏鐩稿叧銆?/span>鏈夌爺绌舵樉绀?/span>锛?/span>浣滀负涓�纰冲寲鍚堢墿锛岀敳閱涜兘澶熻绾冲叆涓�纰冲惊鐜紙one-carbon-cycle锛夛紝鐢ㄤ簬DNA涓?/span>蹇呴渶姘ㄥ熀閰哥殑鍚堟垚锛?/span>Burgos-Barragan, G. et al. Nature, 2017, 548, 549鈥?54锛?/span>銆?/span>铏界劧鐢查啗鐨?/span>杩欎簺鐢熺悊鍔熻兘閫愭笎琚?/span>鎻ず锛?/span>涓庣敳閱涚浉鍏崇殑璁稿鐤戦棶浠?/span>鏈夊緟鎺㈢储銆備緥濡傦紝缁嗚優鏄�氳繃浣曠鏈哄埗鏉?/span>鐗瑰紓璇嗗埆鍜屾劅鐭?/span>鍐呮簮鐢查啗鐨?/span>娴撳害锛?/span>鐢查啗瀵瑰簲鐨勪俊鍙?/span>鏄浣?/span>鍦ㄧ粏鑳炲唴浼犻�?/span>锛?/span>浜х敓鍝嶅簲锛?/span>骞?/span>閬垮厤鐢查啗閫犳垚鐨?/span>鎹熶激锛?/span>鎴?/span>浠張鑳藉惁瀵圭粏鑳炲唴鐨勭敳閱?/span>鍔ㄦ�佸垎甯?/span>杩涜绮惧噯鎺㈡祴锛?/span>浠?/span>鎻ず鐢查啗鐨勭敓鐞嗗姛鑳藉憿锛?/span>
閽堝涓婅堪闂锛?/span>鍖椾含澶у鍖栧涓庡垎瀛愬伐绋嬪闄€�佸寳澶?/span>-娓呭崕鐢熷懡绉戝鑱斿悎涓績闄堥箯璇鹃缁?/span>鐫�鎵嬪涓�涓嫭鐗圭殑鐢查啗鍝嶅簲鐨?/span>杞綍鍥犲瓙HxlR杩涜浜?/span>娣卞叆鐮旂┒锛?/span>棣栨浠庣粨鏋勪笌鍖栧鏈虹悊涓?/span>鎻ず浜?/span>鐢查啗璇卞HxlR铔嬬櫧鍙戠敓鍒嗗瓙鍐呬氦鑱?/span>鍙嶅簲锛?/span>鎵�浜х敓鐨勨�滀簹鐢插熀妗モ�?/span>锛?/span>methylene bridge锛夎繖涓�鐗规畩鍖栧淇グ浣?/span>HxlR浜х敓鍔熻兘鑾峰緱鎬?/span>锛?/span>gain-of-function锛?/span>鐢熺悊鍝嶅簲銆?/span>鍩轰簬杩欎竴鍙戠幇锛?/span>浠栦滑寮�鍙戜簡棣栦釜鍙?/span>閬椾紶缂栫爜鐨勭敳閱涜崸鍏夋帰閽堬紙FAsor锛?/span>锛屾垚鍔熷簲鐢ㄤ簬妫�娴嬫椿缁嗚優浠ュ強灏忛紶鑴戠粍缁囧垏鐗囦腑鐢查啗鐨勫姩鎬佸彉鍖?/span>銆?/span>鐩稿叧鎴愭灉浜?/span>2021骞?/span>1鏈?/span>25鏃?/span>鍦ㄧ嚎鍙戣〃鍦?/span>銆婅嚜鐒?/span>-閫氳銆嬫潅蹇楋紙Nature Communications锛?/span>锛?/span>鈥淕enetically encoded formaldehyde sensors inspired by a protein intra-helical crosslinking reaction鈥?/span> 锛?/span>DOI锛?/span>10.1038/s41467-020-20754-4锛?/span>銆?/span>
鐢查啗瀵?/span>浜?/span>鐢熺墿瀛﹀拰鍖栧棰嗗煙鐨勭爺绌惰�呮潵璇村苟涓嶉檶鐢?/span>銆?/span>濡傛灉鎬濊�冭繖鏍蜂竴涓棶棰?/span>锛?/span>鐢查啗涓庤泲鐧借川浼氬彂鐢熶粈涔?/span>鍖栧鍙嶅簲锛?/span>绛旀鍙兘鏄紝鐢?/span>閱?/span>鑳藉涓?/span>铔嬬櫧璐ㄤ笂鐨勪翰鏍?/span>鎬?/span>姘ㄥ熀閰镐晶閾惧彂鐢熷姞鎴愬弽搴?/span>锛?/span>鐢查啗浣滀负铔嬬櫧璐ㄤ氦鑱旇瘯鍓傦紝鑳藉鍦ㄨ泲鐧借川鐨勪翰鏍?/span>鎬?/span>娈嬪熀锛?/span>濡?/span>璧栨皑閰革級涔嬮棿褰㈡垚浜よ仈锛?/span>浣胯泲鐧借川鍙樻�уけ娲?/span>銆?/span>鐒惰�岋紝鐢查啗浣胯泲鐧借川鍙樻�х殑鍘熷洜涓嶈兘涓?/span>缁嗚優鍝嶅簲鐢查啗鐨勬満鍒?/span>鍒掔瓑鍙?/span>銆?/span>棣栧厛锛?/span>浣胯泲鐧借川鍙樻�х殑鐢查啗娴撳害杩?/span>楂樹簬缁嗚優鍐呮簮鐢查啗鐨?/span>娴撳害鑼冨洿锛?/span>鍏舵锛?/span>鐢查啗浣胯泲鐧借川鍙樻�ф槸涓�绉嶉潪鐗瑰紓鎬х殑銆?/span>鎹熶激鎬х殑杩囩▼锛?/span>杩欏緢闅句綔涓?/span>缁嗚優绮剧‘鍝嶅簲鍜岃皟鎺?/span>鐢熺悊姘村钩鐢查啗鐨?/span>宸ヤ綔鏈哄埗銆?/span>鍥犳锛?/span>鐢查啗鍦ㄧ粏鑳炰腑鏈夊摢浜?/span>鐗瑰紓鎬х殑鍝嶅簲妯″紡锛?/span>杩欎簺鍝嶅簲鏄�氳繃浠�涔堟牱鐨勫垎瀛愭満鍒跺疄鐜扮殑锛?/span>浠嶆槸涓�涓?/span>鏈煡鐨勯棶棰樸�?/span>鍦?/span>鏋崏鑺藉鏉嗚弻鍙戠幇鐨?/span>HxlR铔嬬櫧鏄竴绉嶈浆褰曟縺娲诲洜瀛?/span>锛?/span>鑳藉鍦ㄧ敳閱涘埡婵�涓?/span>婵�娲讳笅娓稿熀鍥犺浆褰曪紝杩涜鍔熻兘鑾峰緱鎬э紙gain-of-function锛夌殑鐢熺悊鍝嶅簲锛?/span>Yurimoto, H. et al. Mol. Microbiol., 2005, 57, 511鈥?19锛?/span>銆?/span>鍙?/span>HxlR杩欎竴鐗规�?/span>鐨?/span>鍚稿紩锛?/span>鐮旂┒鍥㈤槦閫夋嫨HxlR铔嬬櫧浠ユ帰绌?/span>鍏?/span>鈥?/span>鐗瑰紓鈥?/span>鍝嶅簲鐢查啗鍒嗗瓙鐨勬満鍒?/span>銆?/span>
棣栧厛锛屼负浜嗙‘璁?/span>HxlR铔嬬櫧鐩存帴涓庣敳閱涘彂鐢熶簡鍖栧鍙嶅簲锛?/span>鐮旂┒鍥㈤槦缁撳悎璐ㄨ氨鍒嗘瀽涓?/span>X灏勭嚎鏅朵綋瀛?/span>鐮旂┒浜?/span>HxlR涓庣敳閱?/span>鐨勭浉浜掍綔鐢?/span>銆?/span>HxlR涓庣敳閱?/span>鍏卞鑲?/span>鍚?/span>鐨勮川璋卞垎鏋愭樉绀?/span>锛?/span>鐢查啗鑳藉浣?/span>HxlR鍙戠敓+12 Da鐨勫垎瀛愰噺鍋忕Щ銆傝繖涓�鍙樺寲涓?/span>鐢查啗璇卞鐨勪簹鐢插熀妗?/span>杩?/span>涓�鑷达紝璇存槑HxlR寰堟湁鍙兘鐩存帴涓庣敳閱涘彂鐢?/span>浜?/span>鍙嶅簲銆傝繘涓�姝ョ殑浜岀骇璐ㄨ氨鑲芥閴村畾锛屼互鍙?/span>HxlR-鐢查啗鍏辨櫠缁撴瀯瑙ｆ瀽鍏卞悓浣愯瘉浜嗚繖涓�鐐广�?/span>涓よ�呯殑缁撴灉鍧囨樉绀猴紝涓庣敳閱涘弽搴斾箣鍚庯紝浣嶄簬HxlR铔嬬櫧N绔?/span>绗竴涓?/span>伪铻烘棆鐨?/span>鍗婅儽姘ㄩ吀锛?/span>Cys11锛?/span>涓?/span>璧栨皑閰革紙Lys13锛?/span>娈嬪熀涔嬮棿褰㈡垚浜?/span>浣嶇偣鐗瑰紓鐨?/span>鈥滀簹鐢插熀妗モ�?/span>銆?/span>閽堝杩欎竴鍙戠幇锛?/span>鐮旂┒鍥㈤槦鍙堥�氳繃浣嶇偣绐佸彉鏉ョ‘璁?/span>璇?/span>浜よ仈鍙嶅簲涓?/span>HxlR铔嬬櫧鍔熻兘鐨勮仈绯?/span>銆?/span>缁撴灉鏄剧ず锛屾棤璁?/span>绐佸彉鍝?/span>涓�涓綅鐐癸紙C11A鎴?/span>K13A锛夛紝HxlR閮藉皢澶卞幓鍝嶅簲鐢查啗鐨勮兘鍔涖�?/span>杩欒鏄?/span>HxlR铔嬬櫧鐨勭‘閫氳繃Cys11鍜?/span>Lys13鐗瑰紓鎬ц瘑鍒敳閱涳紝褰㈡垚浜氱敳鍩烘ˉ杩欎竴鐙壒鐨?/span>鍖栧淇グ锛?/span>瀹炵幇杞綍鍔熻兘鐨?/span>婵�娲?/span>銆?/span>
鐢查啗涓?/span>HxlR铔嬬櫧浣嶇偣鐗瑰紓鎬?/span>鍙嶅簲褰㈡垚鍒嗗瓙鍐?/span>鈥?/span>浜氱敳鍩烘ˉ鈥?/span>
閭ｄ箞鐢查啗璇卞鐨勫垎瀛愬唴浜よ仈鍙堟槸濡備綍瀹炵幇瀵?/span>HxlR铔嬬櫧鍔熻兘鐨?/span>婵�娲?/span>锛?/span>鐮旂┒鍥㈤槦鎺ヤ笅鏉ヤ粩缁嗗垎鏋愪簡涓嶅悓澶勭悊鏉′欢涓庣獊鍙樹綋鐨?/span>HxlR铔嬬櫧鏅朵綋缁撴瀯銆?/span>閫氳繃瀵?/span>鐢查啗澶勭悊鍓嶅悗鐨?/span>HxlR缁撴瀯瀵规瘮锛?/span>浠栦滑鍙戠幇鐪嬩技绠�鍗曠殑浜氱敳鍩烘ˉ鍗村紩璧蜂簡铔嬬櫧鏁翠綋鏋勮薄鐨勬瀬澶у彉鍖栵紒鐢查啗璇卞鐨?/span>Cys11-Lys13浜氱敳鍩烘ˉ杩娇鍘熸湰浣嶄簬鍚屼竴伪铻烘棆涓や晶鐨?/span>涓?/span>涓皑鍩洪吀渚ч摼鐩镐簰闈犺繎锛?/span>鎵洸浜?/span>伪铻烘棆缁撴瀯锛屽苟鈥滅壍涓�鍙戣�屽姩鍏ㄨ韩鈥濓紝甯﹀姩HxlR铔嬬櫧N绔富閾炬湞鍚戠炕杞紙N-terminal flipping锛夛紝浣垮緱铔嬬櫧鏁翠綋鏋勮薄鍙戠敓鏀瑰彉锛?/span>鏋佸ぇ鍦?/span>澧炲己HxlR铔嬬櫧涓?/span>DNA鐨勭粨鍚堣兘鍔?/span>锛?/span>婵�娲?/span>涓嬫父鍩哄洜鐨勮浆褰?/span>銆?/span>鑷虫锛?/span>鐮旂┒鍥㈤槦鎻ず浜?/span>HxlR鐗瑰紓鎬у搷搴旂敳閱涘苟鍙戠敓缁撴瀯涓庡姛鑳借浆鎹㈢殑鍒嗗瓙鏈哄埗銆?/span>
鐢查啗閫氳繃浣嶇偣鐗瑰紓鐨?/span>浜氱敳鍩烘ˉ杩?/span>婵�娲?/span>杞綍鍥犲瓙HxlR
杩欎竴鐢查啗鍝嶅簲鏈哄埗鐨勮В鏋?/span>杩涗竴姝?/span>涓?/span>鐮旂┒鍥㈤槦鎻愪緵浜?/span>鍚ず锛?/span>HxlR鐗瑰紓鎬у搷搴旂敳閱涚殑鏋勮薄鍙樺寲鍙互鐢ㄤ簬璁捐鐢查啗妫�娴?/span>鐨?/span>鑽у厜鎺㈤拡銆?/span>鐩墠宸?/span>鎶ラ亾鐨勭敳閱涙帰閽堝潎涓哄皬鍒嗗瓙鎺㈤拡锛屾椂绌哄垎杈ㄧ巼涓?/span>缁嗚優銆?/span>缁勭粐鐗瑰紓鎬у彈鍒伴檺鍒讹紝闅句互瀵圭敳閱涚殑缁嗚優鍐呭垎甯冭繘琛岀簿纭娴嬨�?/span>鍩哄洜缂栫爜鐨勮崸鍏夋帰閽堬紝鍦ㄦ椂绌哄垎杈ㄧ殑妫�娴嬨�佸姩鎬佹娴?/span>绛?/span>鏂归潰閮芥洿鏈?/span>浼樺娍锛屼絾閴翠簬鐢查啗鍝嶅簲鏈哄埗鐮旂┒鐨勭己涔忥紝闅句互璁捐鍩轰簬铔嬬櫧璐ㄧ殑鎺㈤拡銆?/span>鑰?/span>HxlR铔嬬櫧鐩稿簲鐢查啗鐨?/span>鍒嗗瓙鏈哄埗鐨勮В鏋愭棤鐤戜负杩欎竴闂鎻愪緵浜嗚В鍐虫柟妗堛�?/span>
鍩轰簬瀵?/span>HxlR铔嬬櫧鐨勭粨鏋勫垎鏋愶紝鐮旂┒鍥㈤槦鍚?/span>HxlR鐗瑰畾浣嶇偣宓屽叆浜嗗缁撴瀯鍙樺寲鏁忔劅鐨勮崸鍏夎泲鐧斤紝骞堕�氳繃绛涢�?/span>鍜屼紭鍖栵紝鎴愬姛寮�鍙戝嚭涓�绯诲垪鏂板瀷鍩哄洜缂栫爜鐨勭敳閱涜崸鍏夋帰閽堛�備粬浠鍏堝湪浣撳瀹為獙涓鎺㈤拡杩涜浜嗚〃寰併�備箣鍚庯紝鐮旂┒鍥㈤槦鍒╃敤璇ユ帰閽堬紝鎴愬姛杩涜浜?/span>缁嗚優鍐呯敳閱涙祿搴︾殑鍔ㄦ�佹娴?/span>锛涢�氳繃澶氳壊鑽у厜鎴愬儚锛屽涓嶅悓浜氱粏鑳炵┖闂?/span>涓?/span>鐢查啗鍙樺寲杩涜浜嗗悓姝?/span>妫�娴?/span>锛?/span>閫氳繃骞叉壈鐢查啗浠ｈ阿閫氳矾锛岃褰曚簡鎺㈤拡瀵?/span>鑳炲唴鐢查啗鐢熺悊娴撳害鍙樺寲鐨勫搷搴?/span>銆?/span>杩涗竴姝ワ紝鐮旂┒鍥㈤槦涓庡寳浜ぇ瀛︽潕姣撻緳璇鹃缁勫悎浣滐紝妫�娴嬩簡璇ユ帰閽堝湪灏忛紶鑴戠粍缁囧垏鐗?/span>涓?/span>瀵圭敳閱涚殑鍔ㄦ�佸搷搴?/span>锛?/span>楠岃瘉浜?/span>璇ユ帰閽堝叿鏈?/span>鍔ㄧ墿缁勭粐姘村钩鐨勫簲鐢?/span>娼滃姏銆?/span>
鍩轰簬鐢查啗鍝嶅簲杞綍鍥犲瓙HxlR铔嬬櫧鐨?/span>鏂板瀷鐢查啗鎺㈤拡
缁间笂锛岃宸ヤ綔瀹炵幇浜?/span>瀵?/span>鈥?/span>鐢查啗鍝嶅簲鈥?/span>铔嬬櫧HxlR鐨?/span>鏈哄埗瑙ｆ瀽锛?/span>鍙戠幇浜嗙敳閱?/span>璇卞HxlR浜х敓鐙壒鍖栧淇グ锛?/span>骞剁敱璇?/span>浜氱敳鍩?/span>妗?/span>寮曡捣鏋勮薄鍙樺寲鍜?/span>婵�娲昏浆褰曡皟鎺х殑鍒嗗瓙鏈哄埗銆?/span>鍙楁鍚彂锛?/span>鐮旂┒鍥㈤槦杩涗竴姝?/span>寮�鍙戜簡棣栦釜閬椾紶缂栫爜鐨?/span>鐢查啗鎺㈤拡锛?/span>涓虹爺绌剁粏鑳炲唴婧愮敳閱涚殑璋冩帶涓庡姛鑳?/span>鎻愪緵浜嗛噸瑕佸伐鍏?/span>銆?/span>
闇�瑕佹寚鍑虹殑鏄紝鏈爺绌跺彂鐜扮殑鈥滃垎瀛愬唴浜よ仈鈥?/span>杩欎竴鐙壒鐨?/span>鍖栧淇グ锛屽彲鑳?/span>涓庤泲鐧介叞鍩哄寲銆佺兎鍩哄寲绛?/span>缈昏瘧鍚庝慨楗?/span>绫讳技锛?/span>鑳藉璋冩帶铔嬬櫧璐ㄧ殑娲绘�?/span>涓庡姛鑳?/span>銆?/span>渚嬪杩?/span>鏈?/span>鏈夌爺绌舵樉绀猴紝绯栭叺瑙ｉ�氳矾鐨勪腑闂翠骇鐗╀笝閰啗锛屽彲浠ュ缁嗚優姘у寲搴旀縺閫氳矾铔嬬櫧KEAP1杩涜鈥滃垎瀛愬唴浜よ仈鈥?/span>淇グ锛屽湪閭昏繎鐨?/span>绮炬皑閰?/span>锛?/span>Arg锛変笌鍗婅儽姘ㄩ吀锛?/span>Cys锛変箣闂?/span>浜х敓浜よ仈锛屽惎鍔ㄤ笅娓稿簲婵�鍝嶅簲锛?/span>Bollong, M. et al. Nature, 2018, 562, 600鈥?/span>604锛?/span>銆?/span>鍙互棰勮,鈥滃垎瀛愬唴浜よ仈鈥?/span>淇グ鐨?/span>绉嶇被銆?/span>鎬ц川涓庡姛鑳?/span>锛?/span>鍊煎緱杩涗竴姝ユ帰绱€�?/span>
闄堥箯璇鹃缁?/span>2012绾у崥澹瘯涓氱敓绁濊瀺宄般�佸紶鍔熶负鍏卞悓绗竴浣滆�?/span>锛?/span>鍖椾含澶у鐢熷懡绉戝瀛﹂櫌銆?/span>鐢熷懡绉戝鑱斿悎涓績鏉庢瘬榫欐暀鎺?/span>鍙婂叾璇鹃缁?/span>2012绾у崥澹瘯涓氱敓浜曟芳瀹屾垚浜?/span>鍔ㄧ墿瀹為獙鍏抽敭鏁版嵁銆?/span>璇ュ伐浣滃緱鍒颁簡鍥藉鑷劧绉戝鍩洪噾濮斻�佺鎶�閮ㄣ�佸寳浜垎瀛愮瀛﹀浗瀹剁爺绌朵腑蹇冧互鍙婂寳澶?/span>-娓呭崕鐢熷懡绉戝鑱斿悎涓績鐨勮祫鍔┿�?/span>
璁烘枃閾炬帴锛?/span>//www.nature.com/articles/s41467-020-20754-4