清华大学颜宁教授Cell Research发表新研究成果

2016-08-04 何嫱 生物通

来自清华大学、剑桥生物医学院的研究人员证实,兰尼碱受体1(RyR1)的中央结构域是远距离变构门控通道开放的传感器。这一研究发现发布在7月29日的《Cell Research》杂志上。


来自清华大学、剑桥生物医学院的研究人员证实,兰尼碱受体1(RyR1)的中央结构域是远距离变构门控通道开放的传感器。这一研究发现发布在7月29日的《Cell Research》杂志上。

领导这一研究的是清华大学的颜宁(Nieng Yan)教授。2007年作为普林斯顿大学博士的颜宁受聘于清华大学医学院,成为清华最年轻的教授、博士生导师。在回国的几年间,颜宁教授研究组主要聚焦于膜蛋白、胆固醇代谢调控通路相关因子的结构生物学研究,在Science、Nature、Cell等杂志上发表多篇重要的论文,并荣获了中国青年女科学家奖、HHMI国际青年科学家奖等奖励。

在肌肉细胞中,当细胞外或者肌质网中的钙离子释放到细胞质时,会引发肌肉的收缩反应。这一过程称为肌肉兴奋收缩(E-C)偶联,是骨骼肌及心肌运动的分子基础。而负责将钙离子从肌质网快速大量释放到胞浆中的是一种称作兰尼碱受体(Ryanodine Receptor,简称RyR)的高通量钙离子通道。

RyRs是目前已知的最大离子通道蛋白。在哺乳动物中有三种RyR蛋白,其中RyR1主要分布在骨骼肌细胞中,RyR2主要分布在心肌细胞中,RyR3则最早在脑细胞中发现。大量文献报道统计表明,目前已有超过500种RyR突变体与疾病有关。

2012年,哥伦比亚大学分子心脏病研究所Andrew R. Marks教授领导研究人员,在早期心脏和肌肉疾病研究基础上,提出了可能是由于海马区RyR2不稳定引发了创伤后应激障碍(PTSD),确定了发生泄漏的RyR2通道是引发与压力有关的认知功能障碍的一个因素。这项研究发表在Cell杂志上。

2014年12月,Nature杂志公布了有关RyRs的两项重要研究成果。在一篇文章中来自哥伦比亚大学的研究人员公布了兔兰尼碱受体2.3兆道尔顿复合物的结构,这一结构的分辨率为4.8Å,通过这一结构,研究人员发现RyR的具体通道构成,包括六个跨膜离子通道超家族。另外一篇文章则利用电子显微镜分析了同样是兔RyR的调控机制,研究人员获得了6.1Å的RyR结构,这两篇文章均为进一步探讨RyR构象开关,作用机制提供了新的信息。

2015年,颜宁研究组与清华大学生命学院施一公研究组、以及英国MRC分子生物学实验室Sjors Scheres研究组合作在Nature杂志发表重要研究成果,揭示出了兔源RyR1的近原子分辨率结构,为理解其功能提供了重要线索。该研究对于肌肉-收缩偶联以及与之相关的疾病的认识也具有重要的意义,为治疗相关疾病提供了重要的结构线索。

在这篇Cell Research新文章中,颜宁教授课题组旨在阐明RyR1的远距离变构门控机制。研究人员报告称采用冷冻电子显微镜获得了分辨率在3.8–4.2埃(Å)之间、处于三种闭合构象的兔RyR1结构,以及分辨率为5.7 Å的开放状态的RyR1结构。比较这些结构提供了有关骨骼肌中肌肉兴奋收缩偶联的一些重要新认识,并揭示出了RyRs的门控机制。

参考文献:

Xiao-Chen Bai1,*, Zhen Yan2,3,4,*, Jianping Wu2,3,4,*, Zhangqiang Li2,3,4 and Nieng Yan2,3,4.The Central domain of RyR1 is the transducer for long-range allosteric gating of channel opening.Cell Research.29 July 2016.

 

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    2017-05-28 维他命
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  4. 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authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/jW482SpianMayicTRbRZ5RzfPkmqRTH5rHib5mcib8Wb3QdXjhfOK1UubQL2lictjJFdFJ6Lc3cnnCOSWqxXZ4Kk6y5GdzDoy764R/0, createdBy=156e1644785, createdName=doctorJiangchao, createdTime=Thu Aug 04 14:23:00 CST 2016, time=2016-08-04, status=1, ipAttribution=)]
    2016-08-06 syscxl
  5. 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    2016-08-06 医生2397
  6. 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    2016-08-06 yangshch
  7. 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    2016-08-05 xmax889

    为这些大牛们电赞,学习的方向

    0

  8. 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channel=null, level=null, likeNumber=34, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=15339, encryptionId=d2601533982, topicName=Research)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=96ab14929432, createdName=yangshch, createdTime=Sat Aug 06 00:59:00 CST 2016, time=2016-08-06, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=96249, encodeId=f2c59624992, content=为这些大牛们电赞,学习的方向, beContent=null, objectType=article, channel=null, level=null, likeNumber=48, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cacheapi.medsci.cn/resource/upload/20160813/IMG57AE8D930B40D3563.jpg, createdBy=13a81695880, createdName=xmax889, createdTime=Fri Aug 05 22:13:00 CST 2016, time=2016-08-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=95991, encodeId=61c7959916c, content=太厉害了, beContent=null, objectType=article, channel=null, level=null, likeNumber=56, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://api.medsci.cn/resource/upload/20150606/IMG557232CB4CF873916.jpg, createdBy=ea561627373, createdName=Kindlyer, createdTime=Thu Aug 04 18:31:00 CST 2016, time=2016-08-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=95975, encodeId=eb87959e539, content=好好好好学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=56, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=45101626056, createdName=忠诚向上, createdTime=Thu Aug 04 17:02:00 CST 2016, time=2016-08-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=95914, encodeId=493395914f3, content=继续学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=50, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/jW482SpianMayicTRbRZ5RzfPkmqRTH5rHib5mcib8Wb3QdXjhfOK1UubQL2lictjJFdFJ6Lc3cnnCOSWqxXZ4Kk6y5GdzDoy764R/0, createdBy=156e1644785, createdName=doctorJiangchao, createdTime=Thu Aug 04 14:23:00 CST 2016, time=2016-08-04, status=1, ipAttribution=)]
    2016-08-04 Kindlyer

    太厉害了

    0

  9. 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channel=null, level=null, likeNumber=34, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=15339, encryptionId=d2601533982, topicName=Research)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=96ab14929432, createdName=yangshch, createdTime=Sat Aug 06 00:59:00 CST 2016, time=2016-08-06, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=96249, encodeId=f2c59624992, content=为这些大牛们电赞,学习的方向, beContent=null, objectType=article, channel=null, level=null, likeNumber=48, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cacheapi.medsci.cn/resource/upload/20160813/IMG57AE8D930B40D3563.jpg, createdBy=13a81695880, createdName=xmax889, createdTime=Fri Aug 05 22:13:00 CST 2016, time=2016-08-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=95991, encodeId=61c7959916c, content=太厉害了, beContent=null, objectType=article, channel=null, level=null, likeNumber=56, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://api.medsci.cn/resource/upload/20150606/IMG557232CB4CF873916.jpg, createdBy=ea561627373, createdName=Kindlyer, createdTime=Thu Aug 04 18:31:00 CST 2016, time=2016-08-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=95975, encodeId=eb87959e539, content=好好好好学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=56, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=45101626056, createdName=忠诚向上, createdTime=Thu Aug 04 17:02:00 CST 2016, time=2016-08-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=95914, encodeId=493395914f3, content=继续学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=50, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/jW482SpianMayicTRbRZ5RzfPkmqRTH5rHib5mcib8Wb3QdXjhfOK1UubQL2lictjJFdFJ6Lc3cnnCOSWqxXZ4Kk6y5GdzDoy764R/0, createdBy=156e1644785, createdName=doctorJiangchao, createdTime=Thu Aug 04 14:23:00 CST 2016, time=2016-08-04, status=1, ipAttribution=)]
    2016-08-04 忠诚向上

    好好好好学习

    0

  10. 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authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/jW482SpianMayicTRbRZ5RzfPkmqRTH5rHib5mcib8Wb3QdXjhfOK1UubQL2lictjJFdFJ6Lc3cnnCOSWqxXZ4Kk6y5GdzDoy764R/0, createdBy=156e1644785, createdName=doctorJiangchao, createdTime=Thu Aug 04 14:23:00 CST 2016, time=2016-08-04, status=1, ipAttribution=)]
    2016-08-04 doctorJiangchao

    继续学习

    0

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