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Nature communications:G蛋白偶联受体信号转导机制取得新进展

2015-09-16 佚名 生物谷

(GPCR)可以说是研究最普遍的一种受体,也是药物开发工作中的重要靶点,据统计超过30%的临床处方药是直接作用在GPCR上的,相关的研究已经获得了10次诺贝尔奖,GPCR的受重视程度可见一斑。GPCR主要通过G蛋白或者Arrestin信号转导行使功能,然而无论是G蛋白还是Arrestin,如何识别特异的受体产生的信号指令,并翻译成下游的功能的机制是不清楚的。 中国科学院生物物理所的王江云课题组

(GPCR)可以说是研究最普遍的一种受体,也是药物开发工作中的重要靶点,据统计超过30%的临床处方药是直接作用在GPCR上的,相关的研究已经获得了10次诺贝尔奖,GPCR的受重视程度可见一斑。GPCR主要通过G蛋白或者Arrestin信号转导行使功能,然而无论是G蛋白还是Arrestin,如何识别特异的受体产生的信号指令,并翻译成下游的功能的机制是不清楚的。

中国科学院生物物理所的王江云课题组和山东大学医学院的孙金鹏课题组于2015年9月8号在权威期刊Nature communications上发表了题为“Phospho-selective mechanisms of arrestin conformations and functions revealed by unnatural amino acid incorporation and 19F-NMR”的研究论文,报道了他们应用最新的非天然氨基酸编码技术,揭示了G蛋白偶联受体重要的信号转导机制的详细过程。。

中科院生物物理所的王江云课题组和山东大学医学院的孙金鹏课题组应用最新的非天然氨基酸编码方法和19FNMR技术,发现Arrestin是通过精确识别受体特异的磷酸化密码信息,来指导下游信号转导的机制,并提出了重要的新的假说。两个联合实验组的研究发现,Arrestin可以通过N端的10个磷酸化位点来识别特异的受体磷酸化编码信息,并产生相应的多种特异性构型变化,从而选择性的结合下游蛋白,产生多种功能。据此结果,联合小组提出了受体信号转导的笛子模型:受体的磷酸化编码产生的花样指导Arrestin的信号时,就像手指按在笛子的孔上,不同的磷酸化组合可以带来不同的手指组合,从而形成特异的音符, 指导Arrestin的多样性功能。一种1-4-6-7的音符可以激活Clathrin, 从而介导受体内吞。而另一种1-5音符可以激活SRC, 促进细胞的迁移等。考虑到10个磷酸化位点的组合可以带来超过1000种变化(210-1=1023),因此受体C末端不同的磷酸化花样就可以引起超过1000种Arrestin的特异性构型;受体在理论上可以通过Arrestin启动超过1000种信号途径。这个新的磷酸化编码理论可以部分解释长期以来的一个悬而未决的问题:人体内超过800个GPCR如何利用仅有的24个效应器蛋白(20个G蛋白,4个Arrestin)行使多种多样的(>10000种)细胞功能。这一研究也将为今后人们更好的设计基于GPCR的药物提供指导。

推荐的英文摘要:

Phospho-selective mechanisms of arrestin conformations and functions revealed by unnatural amino acid incorporation and 19F-NMR.Nature communications.2015 

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    2015-12-05 liye789132251
  5. [GetPortalCommentsPageByObjectIdResponse(id=1811539, encodeId=b29a181153921, content=<a href='/topic/show?id=552688630bf' target=_blank style='color:#2F92EE;'>#蛋白偶联#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=30, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=88630, encryptionId=552688630bf, topicName=蛋白偶联)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=5c0050, createdName=lishiwen, createdTime=Wed Mar 09 20:13:00 CST 2016, time=2016-03-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1813626, encodeId=6dc8181362698, content=<a href='/topic/show?id=9bbe933362a' target=_blank style='color:#2F92EE;'>#转导机制#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=34, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=93336, encryptionId=9bbe933362a, topicName=转导机制)], attachment=null, authenticateStatus=null, createdAvatar=http://thirdqq.qlogo.cn/qqapp/101296147/72D57F5B3E12B2BB53D6BD015D14DCD6/100, createdBy=a92e2500162, createdName=passed water, createdTime=Sat Dec 05 02:13:00 CST 2015, time=2015-12-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1746942, encodeId=80d31e46942f6, content=<a href='/topic/show?id=165b836349' target=_blank style='color:#2F92EE;'>#G蛋白偶联受体#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=44, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=8363, encryptionId=165b836349, topicName=G蛋白偶联受体)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=601235881674, createdName=huiwelcome, createdTime=Fri Apr 29 12:13:00 CST 2016, time=2016-04-29, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1880814, encodeId=bf5018808141c, content=<a href='/topic/show?id=3b2112532d8' target=_blank style='color:#2F92EE;'>#Nat#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=32, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=12532, encryptionId=3b2112532d8, topicName=Nat)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=2e6f107, createdName=liye789132251, createdTime=Sat Dec 05 06:13:00 CST 2015, time=2015-12-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2086825, encodeId=1800208682524, content=<a href='/topic/show?id=490750196b' target=_blank style='color:#2F92EE;'>#COMMUN#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=5019, encryptionId=490750196b, topicName=COMMUN)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=7931272, createdName=liuli5079, createdTime=Mon Jan 25 03:13:00 CST 2016, time=2016-01-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1715524, encodeId=4b151e1552468, content=<a href='/topic/show?id=b1f58362e8' target=_blank style='color:#2F92EE;'>#G蛋白#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=42, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=8362, encryptionId=b1f58362e8, topicName=G蛋白)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=91a331951491, createdName=12498f1em18(暂无昵称), createdTime=Thu Feb 25 09:13:00 CST 2016, time=2016-02-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1573390, encodeId=ad4215e339070, content=<a href='/topic/show?id=28f4125430b' target=_blank style='color:#2F92EE;'>#Nature Communications#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=42, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=12543, encryptionId=28f4125430b, topicName=Nature Communications)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=6bea15872676, createdName=qindq, createdTime=Fri Sep 18 00:13:00 CST 2015, time=2015-09-18, status=1, ipAttribution=)]
    2016-01-25 liuli5079
  6. [GetPortalCommentsPageByObjectIdResponse(id=1811539, encodeId=b29a181153921, content=<a href='/topic/show?id=552688630bf' target=_blank style='color:#2F92EE;'>#蛋白偶联#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=30, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=88630, encryptionId=552688630bf, topicName=蛋白偶联)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=5c0050, createdName=lishiwen, createdTime=Wed Mar 09 20:13:00 CST 2016, time=2016-03-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1813626, encodeId=6dc8181362698, content=<a href='/topic/show?id=9bbe933362a' target=_blank style='color:#2F92EE;'>#转导机制#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=34, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=93336, encryptionId=9bbe933362a, topicName=转导机制)], attachment=null, authenticateStatus=null, createdAvatar=http://thirdqq.qlogo.cn/qqapp/101296147/72D57F5B3E12B2BB53D6BD015D14DCD6/100, createdBy=a92e2500162, createdName=passed water, createdTime=Sat Dec 05 02:13:00 CST 2015, time=2015-12-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1746942, encodeId=80d31e46942f6, content=<a href='/topic/show?id=165b836349' target=_blank style='color:#2F92EE;'>#G蛋白偶联受体#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=44, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=8363, encryptionId=165b836349, topicName=G蛋白偶联受体)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=601235881674, createdName=huiwelcome, createdTime=Fri Apr 29 12:13:00 CST 2016, time=2016-04-29, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1880814, encodeId=bf5018808141c, content=<a href='/topic/show?id=3b2112532d8' target=_blank style='color:#2F92EE;'>#Nat#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=32, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=12532, encryptionId=3b2112532d8, topicName=Nat)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=2e6f107, createdName=liye789132251, createdTime=Sat Dec 05 06:13:00 CST 2015, time=2015-12-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2086825, encodeId=1800208682524, content=<a href='/topic/show?id=490750196b' target=_blank style='color:#2F92EE;'>#COMMUN#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=5019, encryptionId=490750196b, topicName=COMMUN)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=7931272, createdName=liuli5079, createdTime=Mon Jan 25 03:13:00 CST 2016, time=2016-01-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1715524, encodeId=4b151e1552468, content=<a href='/topic/show?id=b1f58362e8' target=_blank style='color:#2F92EE;'>#G蛋白#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=42, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=8362, encryptionId=b1f58362e8, topicName=G蛋白)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=91a331951491, createdName=12498f1em18(暂无昵称), createdTime=Thu Feb 25 09:13:00 CST 2016, time=2016-02-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1573390, encodeId=ad4215e339070, content=<a href='/topic/show?id=28f4125430b' target=_blank style='color:#2F92EE;'>#Nature Communications#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=42, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=12543, encryptionId=28f4125430b, topicName=Nature Communications)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=6bea15872676, createdName=qindq, createdTime=Fri Sep 18 00:13:00 CST 2015, time=2015-09-18, status=1, ipAttribution=)]
  7. [GetPortalCommentsPageByObjectIdResponse(id=1811539, encodeId=b29a181153921, content=<a href='/topic/show?id=552688630bf' target=_blank style='color:#2F92EE;'>#蛋白偶联#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=30, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=88630, encryptionId=552688630bf, topicName=蛋白偶联)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=5c0050, createdName=lishiwen, createdTime=Wed Mar 09 20:13:00 CST 2016, time=2016-03-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1813626, encodeId=6dc8181362698, content=<a href='/topic/show?id=9bbe933362a' target=_blank style='color:#2F92EE;'>#转导机制#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=34, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=93336, encryptionId=9bbe933362a, topicName=转导机制)], attachment=null, authenticateStatus=null, createdAvatar=http://thirdqq.qlogo.cn/qqapp/101296147/72D57F5B3E12B2BB53D6BD015D14DCD6/100, createdBy=a92e2500162, createdName=passed water, createdTime=Sat Dec 05 02:13:00 CST 2015, time=2015-12-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1746942, encodeId=80d31e46942f6, content=<a href='/topic/show?id=165b836349' target=_blank style='color:#2F92EE;'>#G蛋白偶联受体#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=44, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=8363, encryptionId=165b836349, topicName=G蛋白偶联受体)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=601235881674, createdName=huiwelcome, createdTime=Fri Apr 29 12:13:00 CST 2016, time=2016-04-29, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1880814, encodeId=bf5018808141c, content=<a href='/topic/show?id=3b2112532d8' target=_blank style='color:#2F92EE;'>#Nat#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=32, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=12532, encryptionId=3b2112532d8, topicName=Nat)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=2e6f107, createdName=liye789132251, createdTime=Sat Dec 05 06:13:00 CST 2015, time=2015-12-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2086825, encodeId=1800208682524, content=<a href='/topic/show?id=490750196b' target=_blank style='color:#2F92EE;'>#COMMUN#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=5019, encryptionId=490750196b, topicName=COMMUN)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=7931272, createdName=liuli5079, createdTime=Mon Jan 25 03:13:00 CST 2016, time=2016-01-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1715524, encodeId=4b151e1552468, content=<a href='/topic/show?id=b1f58362e8' target=_blank style='color:#2F92EE;'>#G蛋白#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=42, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=8362, encryptionId=b1f58362e8, topicName=G蛋白)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=91a331951491, createdName=12498f1em18(暂无昵称), createdTime=Thu Feb 25 09:13:00 CST 2016, time=2016-02-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1573390, encodeId=ad4215e339070, content=<a href='/topic/show?id=28f4125430b' target=_blank style='color:#2F92EE;'>#Nature Communications#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=42, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=12543, encryptionId=28f4125430b, topicName=Nature Communications)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=6bea15872676, createdName=qindq, createdTime=Fri Sep 18 00:13:00 CST 2015, time=2015-09-18, status=1, ipAttribution=)]
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