English
聯系我們
網站地圖
郵箱
舊版回顧



我國科學家為活細胞蛋白質安裝“調控開關”

文章來源:光明日報 晉浩天   發布時間:2019-05-10  【字號:     】  

  北京大學化學與分子工程學院、合成與功能生物分子中心陳鵬課題組與王初課題組,8日在《自然》雜志在線發表題為《基于鄰近脫籠技術的活體內蛋白質瞬時激活》的研究論文,報道了兩個課題組合作發展的一種在活體環境下瞬時激活蛋白質的化學生物學新技術。

  在活細胞等生理環境下開展蛋白質功能的原位研究具有重要的科學意義。陳鵬課題組長期致力于發展蛋白質的原位激活技術,希望為活細胞內的每一個蛋白質安裝“調控開關”。最近,他們與王初課題組展開合作,提出并發展了一種蛋白質“鄰近脫籠”策略,將可遺傳編碼的非天然氨基酸脫籠技術與計算機輔助設計篩選技術相結合,在一系列不同種類的蛋白質上實現了高時間分辨的原位激活,為在活細胞及活體動物內研究蛋白質的動態調控機制提供了一種普適性技術。利用這一被命名為CAGE-prox的新方法,他們建立并驗證了“激酶正交激活和信號轉導調控”“時間分辨的蛋白質組學分析”“基于毒素蛋白的抗腫瘤蛋白前藥”等一系列原創應用,展示了這一化學生物學新技術在開展蛋白質動態功能研究與調控中的優勢和特色。

  陳鵬課題組先前提出的“化學脫籠”策略,可通過對蛋白質關鍵殘基的化學保護和脫保護反應,實現對其活性的“關-開”調控。利用這一技術,他們先后在賴氨酸、酪氨酸等天然氨基酸側鏈上實現了生物正交斷鍵反應和化學脫籠,開展了激酶等蛋白質家族的特異激活和機制研究。由于細胞內蛋白質的種類繁多、活性調控機制各異,目前該方法仍受可供脫籠的氨基酸種類限制,無法適用于所有蛋白質。

  為了解決這一問題,陳鵬課題組與王初課題組合作提出了“鄰近脫籠”的新策略,通過向蛋白質活性中心附近引入一種帶有光保護基團的非天然酪氨酸,可同樣實現對其活性的遠程干擾和抑制;隨后通過“光脫籠”反應將保護基團移除,使其活性重新恢復。由于在蛋白質活性口袋附近插入非天然酪氨酸后能夠通過影響蛋白穩定性、底物結合等多種因素調控蛋白質活性,該策略將原有的“活性位點脫籠”轉變為“活性口袋脫籠”,極大地擴展了該方法的適用范圍。

  中科院院士、北京大學醫學部教授張禮和表示,陳鵬課題組此前率先利用基于生物正交斷鍵反應的化學脫籠策略,結合遺傳密碼子拓展技術,實現了在蛋白質催化位點的生物正交脫籠,進而原位激活其功能。在最新的工作中,陳鵬課題組與北大王初課題組合作,進一步提出并發展了“鄰近脫籠”的新策略,利用計算機輔助設計與篩選,將蛋白質脫籠技術的適用范圍從催化位點拓展至整個活性口袋,獲得了具有廣泛適用性的蛋白質激活新方法。該工作是化學生物學領域的一項重要進展,為在活細胞及活體動物內開展蛋白質動態功能研究提供了關鍵技術,也為生物正交反應開拓了新的前沿方向。

  據悉,北京大學前沿交叉學科研究院博士畢業生王杰、化學與分子工程學院博士后劉源、研究生劉衍軍為該論文共同第一作者,陳鵬教授和王初研究員為本文的共同通訊作者。該項工作得到了國家自然科學基金委、科技部、教育部、北京分子科學國家研究中心和北大—清華生命科學聯合中心的資助。




(責任編輯:侯茜)

附件:

專題推薦

相關新聞


© 1996 - 中國科學院 版權所有 京ICP備05002857號  京公網安備110402500047號  聯系我們

地址:北京市三里河路52號 郵編:100864

彩之家www.06czj.com www.12sl.com | 凤凰彩票www.3479c.com | www.qj67.com | www.66nb.com | www.279928.com | www.853557.com | 416696.com | www.dl03.com | www.5797.pw | 433345.com | 427786.com | www.726793.com | www.2363.com | www.u69.me | www.338717.com | www.731535.com | www.821124.com | www.898313.com | www.183267.com | 627720.com | tq54.com | 586247.com | www.63hm.com | 三星娱乐www.sxyl4.com | www.362.me | www.953363.com | www.474805.com | 550471.com | www.226.cm | 751264.com | www.746577.com | www.6005.me | www.8791.net | www.076700.com | www.075560.com | www.812082.com | www.981470.com | 465338.com | www.254067.com | www.369092.com | www.44hy.com | www.0367.me | www.89471.com | www.122847.com | www.222346.com | www.953947.com | www.34404.com | www.485737.com | www.847163.com | www.332975.com | 500万彩票www.96386z.com | www.257629.com | www.474618.com | www.51507.com | www.583917.com | www.909511.com | www.254026.com | www.78130.com | www.019015.com | 739394.com | www.jw11.cc | www.139501.com | www.45394.com | www.065566.com | www.200170.com | www.768162.com | www.673728.com | www.961763.com | www.001964.com | www.585022.com | www.7629.cc | www.947362.com | www.69110.com | www.958773.com | www.rr90.com | www.060670.com | www.vj49.com | www.5ye.cc | www.026488.com | www.49go.com | www.920208.com | www.c75.cc | www.700605.com | www.bs58.cc | www.1851.cm | www.089002.com | www.505699.com | www.886992.com | www.956702.com | www.29ew.com | www.403000.com | www.586910.com | www.635343.com | www.930675.com | 545992.com | www.095340.com | www.173188.com | www.576811.com | 多乐彩票www.544646.com | www.ej50.com | www.585579.com | www.588838.com | www.761258.com | www.589676.com | www.ih84.com | www.1369.win | 966957.com | 531265.com | www.773166.com | www.653579.com | www.396232.com | www.08hk.com | www.43pn.com | www.275791.com | www.59116.cc | www.188188.com | 658665.com | www.5219.org | www.3605.cn | www.42wt.com | www.5152.in | www.872314.com | www.923272.com | 703684.com | 584442.com | www.5179.online | www.098731.com | www.110207.com | www.325225.com | www.510439.com | www.et07.com | www.8372.cc | www.6024.org | www.025634.com | www.200262.com | www.251086.com | www.912816.com | www.105801.com | 610029.com | www.699107.com | 500彩票网www.843933.com | www.5337.in | www.08sw.com | www.5239.cm | 447409.com | www.dj60.cc | 969421.com | www.757344.com | www.388963.com | www.88347.com | 6867.biz | www.582282.com | www.61170.com | www.055329.com | www.178095.com | www.724777.cc | www.47354.com | www.530088.com | 450542.com | www.9925.loan | www.948916.com | www.956047.com | www.uh17.com | www.0069.pw | www.97818.com | www.365220.cc | www.836254.com | www.969776.com | www.6778.cm | www.48ch.com | www.900365.cc | www.ro22.com | 345933.com | www.80704.com | www.799660.com | 760152.com | www.652766.com | www.jb71.com | www.330032.com | www.ar20.com | www.15ob.com | 028950.com | www.803477.com | www.194636.com | www.249122.com | www.1494.xyz | www.11538.com | 亿彩www.6832q.com | 272498.com | www.733731.com | www.123479.cc | www.521242.com | www.1zl.cc | www.1226.win | www.5143.top | www.419.online | www.663.win | www.422791.com | 192796.com | www.4028.net | www.455422.com | www.795091.com | www.120361.com | www.642510.com | qw26.com | www.607313.com | www.715702.com | www.083178.com | www.306517.com | www.143460.com | www.755486.com | www.796493.com | www.351375.com | www.478600.com | www.808713.com | www.858914.com | www.59jw.com | www.7471.cm | www.ve06.com | www.914.mobi | www.87rz.com | www.80748.com | www.467262.com | www.017204.com | www.310303.com | www.366011.com | www.005828.com | www.690326.com | 云博彩票www.www.985576.com | www.54bn.com | www.9883.com | www.348548.com | www.921445.com | www.042030.com | www.662601.com | 104144.com | www.l09.cn | www.900181.com | www.526362.com | 483245.com | www.692566.com | www.071.cn | www.0143.win | www.7591.net | www.635634.com | www.385439.com | www.8896.in | www.162001.com | www.76xo.com | www.058369.com | www.234550.com | www.5080.website | www.wi41.com | www.03788.cc | www.544115.com | www.862771.com | www.18310.cc | www.118350.com | www.0dc.com | www.30411.com | www.217579.com | www.432507.com | www.579483.com | 412530.com | www.df92.com | www.43245.com | www.qi82.com | www.002329.com | www.91145.com | www.619107.com | www.126194.com | www.183092.com | www.841539.com | www.217165.com | www.639140.com | www.818526.com | www.av5.com | 凤凰彩票www.66652g.com | 38345.com | www.583856.com | www.254056.com | www.382259.com | www.328768.com | 650952.com | www.si12.com | www.397501.com | www.25112.com | www.233899.cc | www.776508.com | 659447.com | www.rc.com | www.558208.com | www.49064.com | www.63667.com | www.bd84.com | www.39527.cc | 爱购彩票www.335274.com | www.909632.com | www.3660.cc | www.0586.me | www.19226.cc | 爱彩乐www.343918.com | www.136408.com | www.639268.com | www.187853.com | www.509003.com | www.1703.org | www.311757.com | www.083288.com | www.384186.com | www.924288.com | www.558208.com | www.928032.com | 077576.com | 975293.com | 026427.com | 954487.com | 401440.com | www.857466.com | 993678.com | www.090887.com | www.056498.com | 亚投彩票www.ya013.com | www.338800.com | www.504308.com | www.273632.com | www.ta06.com | www.62hp.com | 029230.com | www.997854.com | www.2019.org | www.127352.com | www.721201.com | www.tv46.com | www.719244.com | www.03131.cc | www.30632.com | www.238509.com | 452971.com | www.033971.com | 773038.cc | www.38156.cc | www.065819.com | www.300883.com | www.954031.com | www.6134.biz | www.go39.com | www.959050.com | 网易彩票www.36788z.com | www.2663.in | www.459.xyz | www.168945.com | 792055.com | www.dz90.com | www.620693.com | 338760.com | 965014.com | 全民乐彩票www.qml5.com | www.3314.biz | www.t71.com | www.110861.com | www.8367.biz | www.240729.com | www.667118.com | www.679112.com | www.lq06.com | JJ彩票www.39459.cc | www.636717.com | www.v38.me | www.881599.com | www.18195.cc | www.17735.com | www.562935.com | www.005821.com | www.279260.com | 609440.com | www.852313.com | 653982.com | www.0150.vip | www.175371.com | www.537592.com | www.818033.com | www.738110.com | www.245168.com | 849133.com | www.610356.com | www.320099.com | www.213.red | 670404.com | www.df99.com | www.22rh.com | www.747666.com | du06.com | www.hk22.com | www.tl78.com | www.uf2.cc | 325369.com | www.x91.club | www.923660.com | 509449.com | www.95nd.com | 643121.com | 126彩票网www.745126.com | www.571783.com | www.332314.com | www.311123.com | www.936117.com | www.394588.com | www.166987.com | www.642223.com | www.is25.com | www.436611.com | www.318633.com | www.1972.shop | www.01050.com | www.cai2222.com | www.037368.com | www.4kj.cc | www.22pk.com | pj57.cc | 88683.com | www.hb34.com | 56706.com | www.576939.com | 976273.com | www.19ns.com | www.874384.com | 500彩票www.375477.com | www.163539.com | 796446.com | 723562.com | www.059289.com | www.173961.com | www.66dsy.com | www.53351.com | www.55373.cc | 295972.com | www.fw10.com | 96ii.com | www.212282.com | 680342.com | www.393600.com | www.611961.com | www.455075.com | www.38834.com | 828463.com | 984065.com | www.425915.com | www.165.win | www.gj60.com | www.684442.com | www.953269.com | www.s01.website | www.060.cx | www.017907.com | www.143320.com | www.19810.com | www.019391.com | www.839423.com | www.949597.com | 58591.com | 348989.com | www.88359.cc | www.1954.date | www.926183.com | 840021.com | www.206104.com | www.642733.com | www.1184.vip | www.1679.org | www.121604.com | www.63122.com | www.499114.com | www.602428.com | www.91670.com | 83pn.com | www.320007.com | www.w68.org | www.143533.com | www.3816.me | www.287618.com | www.77351.com | www.141959.com | www.325845.com | www.386486.com | www.777514.com | www.174520.com | www.1140.cn | www.2431.cc | www.306226.com | www.650096.com | www.304688.com | www.3al.com | www.892611.com | www.679055.com | www.804415.com | www.bu20.com | www.770268.com | www.180373.com | 500彩票网www.61655o.com | 62409.com | 537235.com | www.cp99.com | www.199751.com | www.890711.com | 173935.com | 406466.com | www.35092.com | www.4271.vip | www.1152.org | www.520669.com | zx64.com | www.954980.com | www.724756.com | www.45266.cc | 561478.com | www.745248.com | www.998265.com | www.9692.org | www.z13.me | 082768.com | www.909395.com | 971034.com | www.882528.com | 476632.com | www.96739.cc | www.93208.com | www.839441.com | www.972988.com | www.288169.com | www.507395.com | www.cp0417.com | www.5827.wang | www.615682.com | www.533150.com | 博友彩www.193629.com | www.xpj68.co | www.201343.com | www.229321.com | www.sy20.cc | www.cp7228.com | www.643422.com | 609575.com | 654801.com | www.116207.com | www.138658.com | www.311369.comm | 972341.com | www.581361.com | www.jw52.com | www.353.club | www.456559.com | www.219646.com | www.215581.com | www.8809.com | www.162.loan | www.55mv.com | www.066982.com | www.954756.com | www.874151.com | www.241105.com | www.61466.cc | www.286114.com | www.517245.com | www.985485.com | 744739.com | www.111583.com | www.374918.com | www.1055.com | www.mm54.com | www.457979.com | www.585979.com | www.156992.com | www.990125.com | 4012.biz | 9339.cc | www.896225.com | www.595882.com | 038840.com | 718536.com | www.952852.com | www.982401.com | www.7056.vip | 08578.com | www.374342.com | www.v69.top | www.5538.vip | 232792.com | gi06.com | www.876714.com | www.6of.com | www.cai1147.com | www.r49.cc | www.530757.com | www.749567.cc | 761021.com | 995404.com | www.644248.com | 789434.com | www.510110.com | www.81fn.com | www.99983.cc | www.485355.com | www.66219.cc | 984172.com | 109446.com | www.670119.com | www.972204.com | www.5032.vip | www.ga54.com | www.19810.com | www.83929.cc | www.594979.com | www.0hr.com | 719781.com | 七彩www.53900g.com | www.177075.com | www.553927.com | www.369260.com | www.181389.com | www.303284.com | www.927580.com | 964081.com | 081146.com | www.669447.com | www.137.mobi | www.163626.com | 818合彩www.07hc.com | www.87770.com | www.222881.com | www.745602.com | www.963772.com | www.507188.com | www.982711.com | www.586440.com | 110084.com | www.gz76.com | www.607969.com | 10559.com | 019439.com | www.878574.com | 654473.com | www.896954.com | www.ab41.com | www.410092.com | www.05701.com | www.073211.com | www.016339.com | www.111197.com | www.450058.com | 彩之堂www.55czt.com | www.206294.com | www.238978.com | www.124012.com | www.183033.com | www.805762.com | 92cc.cc | www.088429.com | www.0807.vip | www.124871.com | www.174678.com | www.14az.com | 幸运彩票www.73166g.com | www.pq1.com | 金彩www.987jc.com | www.74442.cc | 109446.com | www.989456.com | www.023137.com | www.617.cm | www.80eu.com | 5504.live | www.989276.com | 329381.com | www.433066.com | www.26bd.com | www.313603.com | www.776803.com | www.871582.com | www.631309.com | www.73213.com | www.34372.com | www.48245.com | 426986.com | www.356503.com | www.049876.com | www.770881.com | 729585.com | www.113959.com | www.7617.org | www.121705.com | www.453545.com | www.4331.vip | www.8414.xyz | www.346811.com | www.395666.com | www.557508.com | 960434.com | www.871726.com | www.76ym.com | 029550.com | www.986673.com | 654777.com | www.795234.com | www.960506.cc | www.595502.com | www.040298.com | www.77665.com | www.598413.com | 03862.com | 472148.com | www.791483.com | www.911348.com | www.516289.com | www.521136.com | www.313782.cc | www.298836.com | www.010.red | www.708972.com | www.55844.cc | www.755257.com | 969690.com | www.742919.com | 749338.com | www.953265.com | www.202360.com | www.134517.com | www.444077.com | www.515576.com | 963426.com | www.974805.com | 980964.com | www.326863.com | www.227706.com | www.422703.com | www.924646.com | www.703098.com | 395227.com | 765548.com | www.cai5522.com | 898959.com | www.57bw.com | www.298876.com | www.46jo.com | 798168.com | www.404000.cc | 07576.com | www.092269.com | www.208257.com | www.87of.com | www.5998.site | www.974162.com | www.19958.com | www.13326.cc | www.8149.com | www.395336.com | www.dm30.com | www.kz6.cc | www.761911.com | 037307.com | www.01216.com | 492882.com | www.02644.com | www.077422.com | www.949358.com | 332516.com | www.47hq.com | www.211195.com | www.786018.com | 426986.com | www.589713.com | www.cb16.com | www.36lq.com | www.898000.com | www.1674.me | www.091045.com | www.003500.com | www.171107.com | www.4345.com | www.68611.cc | www.698272.com | 776991.com | www.k11.wang | www.299682.com | www.481156.com | www.103355.com | www.422445.com | www.866114.com | www.340059.com | www.261806.com | www.802072.com | www.cp695.com | www.114831.com | www.yp35.com | www.481958.com | www.966130.com | www.250008.com | www.004655.com | 58en.com | www.067577.com | www.029959.com | www.053660.com | www.cp902.com | www.334133.com | www.y35.cn | 106064.com | www.169592.com | www.173652.com | www.76081.com | www.762407.com | www.7687.vip | www.03960.com | www.767267.com | www.883732.com | www.737686.com | www.959719.com | 894801.com | www.733008.com | www.9qe.com | www.228013.com | www.397146.com | www.579808.com | www.8675.in | www.009646.com | www.444534.com | www.35680.cc | 639942.com | www.tm67.com | www.4ic.com | www.so02.com | 959646.com | www.833787.com | 588281.com | www.67mw.com | www.39995.com | www.ik53.com | 122872.com | www.641605.com | www.175020.com | www.518028.com | www.520054.com | www.51qq.com | www.183051.com | www.726755.com | 1148.pw | www.78758.cc | 242087.com | www.689.live | 亚投彩票www.ya466.com | jz77.cc | www.62620.cc | www.i27.in | 380321.com | www.72lu.com | www.869553.com | www.793828.com | www.714305.com | www.146533.com | www.36tx.com | www.926668.cc | www.870674.com | www.85517.cc | www.093868.com | www.77785.com | www.339088.com | www.7186.pw | www.4787.cn | www.0515.cn | www.15551.com | www.ru35.com | www.956609.com | 501260.com | www.hb41.com | 696793.com | 217597.com | www.752665.com | www.72wh.com | www.095771.com | www.dy96.com | www.957435.com | www.126612.com | 392981.com | 854609.com | 686944.com | www.633821.com | www.752853.com | www.36653.cc | www.325923.com | www.027106.com | www.237584.com | www.730096.com | www.048929.com | www.374437.com | www.083179.com | www.581602.com | www.92137.cc | www.322245.com | www.616745.com | www.241698.com | www.711611.com | www.034916.com | 121432.com | 50294.com | 凤凰彩票www.88266r.com | 263535.com | 539048.com | www.890996.com | www.99453.com | 634782.com | www.085010.com | www.908742.com | www.905756.com | 772439.com | www.439488.com | www.630167.com | www.719608.com | www.62cw.com | www.186896.com | www.444315.com | www.23885.com | www.76792.cc | www.269555.com | www.49931.com | www.ik3.com | www.3354.cn | www.cp347.com | 大玩家彩票www.9478b.com | 115480.com | www.613402.com | www.111377.com | www.047896.com | www.125605.com | www.218229.com | 948047.com | www.20908.cc | www.271762.com | 904148.com | 101442.com | www.021567.com | www.800051.cc | 657340.com | www.988982.com | www.769465.com | xn41.com | www.75699.cc | www.986304.com | www.717103.com | www.u44.bid | 751130.com | www.889933.cc | www.019631.com | www.248099.com | www.028375.com | www.057391.com | www.565236.com | www.142073.com | www.573480.cc | 中国福利彩票www.3478a.cc | www.911842.com | www.72up.com | www.393422.com | www.088270.com | 654804.com | www.642474.com | www.277717.com | www.563221.com | www.853149.com | 723956.com | 611397.com | 369424.com | www.825018.com | 273617.com | 736912.com | www.169617.com | www.414849.com | www.321446.com | www.275962.com | www.459186.com | www.60610.com | www.90902.cc | www.158470.com | 023027.com | www.681002.com | 966621.com | 802304.com | 121493.com | oz45.com | www.654475.com | www.823522.com | www.220152.com | 249797.com | www.809695.com | www.595604.com | www.34907.com | www.271673.com | www.077569.com | www.147285.com | www.182394.com | www.444123.cc | www.391928.com | www.756188.com | 681690.com | www.305500.com | 666206.com | www.819581.com | www.17164.com | pk99.com | 129171.com | www.507967.com | www.70106.com | www.948117.com | www.400738.com | www.9671.me | www.383608.com | www.800717.com | www.297631.com | 351532.com | www.136154.com | www.119803.com | www.571619.com | 894218.com | www.ae68.cc | 685703.com | 863072.com | 965427.com | www.823727.com | www.461883.com | www.416633.com | www.30733.com | www.es10.com | www.76jl.com | www.509325.com | www.222001.com | www.22310.com | www.565862.com | www.k81111.com | 487680.com | www.85sq.com | www.230618.com | 658415.com | cai2341.com | www.973074.com | www.738631.com | www.003492.com | www.15240.cc | www.20465.com | www.172128.com | www.606423.com | 350652.com | 725681.com | 800842.com | 彩票大家乐www.21202j.com | www.365189.cc | 945633.com | www.7896.org | www.956873.com | 741882.com | www.h37.com | www.75cr.com | www.183359.com | www.m80.pw | www.190056.com | www.060111.com | www.40655.com | www.110547.com | www.98762.cc | www.019913.com | www.006548.com | www.898887.com | www.557822.com | www.707378.com | www.65277.cc | www.18771.com | www.40gk.com | www.9547.cc | www.144875.com | www.37183.com | www.336382.com | www.220971.com | www.85725.cc | www.04kr.com | 中彩网www.91233b.com | 1号彩票www.yi648.com | www.669092.com | www.553541.com | www.601396.com | 856525.com | 481286.com | www.180808.com | www.929633.com | 247985.com | www.791140.com | www.691995.com | www.801018.com | www.679085.com | www.2286.pw | www.8363.biz | www.83rt.com | www.487641.com | www.276068.com | www.012865.com | www.1216.la | www.219832.com | www.523951.com | www.708311.com | www.754747.com | 爱购彩票www.335294.com | www.95000.cc | www.562110.com | 015830.com | www.190208.com | 076963.com | www.uj8.com | 中华彩票www.914979.com | www.922921.com | 多乐彩票www.854242.com | 63911.com | 192675.com | 632569.com | www.955943.com | www.521890.com | www.999884.com | www.760926.com | www.311851.com | 352592.com | www.967614.com | 金掌柜www.83993k.com | www.831102.com | www.78pd.com | 150735.com | www.8716.xyz |