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PCR二聚体形成需要胆固醇当“胶水”

2016-11-06 佚名 生物谷

最近一项发表在国际学术期刊PLOS Computational Biology上的新研究发现,胆固醇或可作为选择性“胶水”将两个蛋白质结合在一起形成配对结构,帮助细胞应答外部信号。G蛋白偶联受体(GPCR)是位于真核细胞外膜上的一个膜蛋白家族。GPCR能够感受细胞外部信号,如激素或糖分子,然后将信号转化为细胞内应答反应。为了能够正确感知和应答外部信号,有证据表明一些GPCR必须配对形成二聚体蛋白结


最近一项发表在国际学术期刊PLOS Computational Biology上的新研究发现,胆固醇或可作为选择性“胶水”将两个蛋白质结合在一起形成配对结构,帮助细胞应答外部信号。

G蛋白偶联受体(GPCR)是位于真核细胞外膜上的一个膜蛋白家族。GPCR能够感受细胞外部信号,如激素或糖分子,然后将信号转化为细胞内应答反应。为了能够正确感知和应答外部信号,有证据表明一些GPCR必须配对形成二聚体蛋白结构来发挥作用。

在这项新研究中,来自德国的研究人员利用一个叫做CXCR4(chemokine receptor type4)的GPCR在分子水平上研究二聚体的形成。他们进行了超过1000次计算机模拟来研究细胞膜上与CXCR4临近的分子,比如胆固醇,如何影响二聚体形成。

模拟结果表明CXCR4需要胆固醇来使两个蛋白正确配对。胆固醇分子能够选择性地将两个CXCR4分子“胶合”在一起形成一种能够感知和传递外部信号的结构。CRCR4分子周围如果没有足够的胆固醇,两个分子仍然能够结合在一起,但是形成的畸形结构可能无法感知信号。

正常来说,CXCR4能够帮助人体免疫系统行使正常功能。但是该蛋白也在转移性乳腺癌和肺癌以及艾滋病中发挥主要作用。科学家们估计有大约40%的处方药都作用于GPCR,因此准确理解胆固醇如何影响GPCR二聚体形成或将开启药物开发的新道路。

原始出处

Pluhackova K, Gahbauer S, Kranz F, Wassenaar TA, Böckmann RA.Dynamic Cholesterol-Conditioned Dimerization of the G Protein Coupled Chemokine Receptor Type 4.PLOS Computational Biology.2016

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    2017-06-11 hxj0117
  3. [GetPortalCommentsPageByObjectIdResponse(id=1995859, encodeId=5afb1995859d0, content=<a href='/topic/show?id=f1af13869e1' target=_blank style='color:#2F92EE;'>#PCR二聚体#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=51, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=13869, encryptionId=f1af13869e1, topicName=PCR二聚体)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=dc7a157, createdName=jinweidong, createdTime=Thu Oct 19 10:33:00 CST 2017, time=2017-10-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1950348, encodeId=c37a1950348d6, content=<a href='/topic/show?id=bfc624041dc' target=_blank style='color:#2F92EE;'>#二聚体#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=55, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=24041, encryptionId=bfc624041dc, topicName=二聚体)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=ac59108, createdName=hxj0117, createdTime=Sun Jun 11 23:33:00 CST 2017, time=2017-06-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1419380, encodeId=9ff31419380bd, content=<a href='/topic/show?id=e290138682e' target=_blank style='color:#2F92EE;'>#PCR#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=57, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=13868, encryptionId=e290138682e, topicName=PCR)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=9cc43496966, createdName=Tommy1950, createdTime=Tue Nov 08 08:33:00 CST 2016, time=2016-11-08, status=1, ipAttribution=)]
    2016-11-08 Tommy1950
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