A novel motif in the yeast mitochondrial dynamin Dnm1 is essential for adaptor binding and membrane recruitment.

A novel motif in the yeast mitochondrial dynamin Dnm1 is essential for adaptor binding and membrane recruitment.
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DOI:
10.1083/jcb.201207079
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发表时间:
2012-11-12
期刊:
The Journal of cell biology
影响因子:
--
通讯作者:
Shaw JM
Shaw JM
中科院分区:
其他
文献类型:
--
作者:
Bui HT;Karren MA;Bhar D;Shaw JM

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在线粒体动力蛋白Dnm 1的插入B结构域中的一个新的基序是在线粒体分裂期间与其适配器Mdv 1相互作用所必需的。为了启动线粒体分裂,动力蛋白相关蛋白(DRPs)必须结合线粒体外膜上的特异性衔接子。这种相互作用背后的结构特征知之甚少。使用酵母作为模型,我们表明,插入B域的Dnm 1鸟苷三磷酸酶(一个DRP)包含一个新的主题所需的协会与线粒体适配器Mdv 1。该保守基序的突变特异性地破坏Dnm 1-Mdv 1相互作用,阻断Dnm 1募集和线粒体分裂。Mdv 1中恢复Dnm 1-Mdv 1相互作用和分裂的抑制突变鉴定了Mdv 1 β-螺旋桨结构域上的潜在蛋白结合界面。这些结果定义了DRP-接头相互作用中插入物B的第一个已知功能。基于插入B结构域和接头蛋白的变异性,我们认为插入B结构域和线粒体接头蛋白是协同进化的,以满足不同生物体对线粒体分裂的独特要求。
A novel motif in the Insert B domain of the mitochondrial dynamin Dnm1 is essential for interaction with its adaptor Mdv1 during mitochondrial fission. To initiate mitochondrial fission, dynamin-related proteins (DRPs) must bind specific adaptors on the outer mitochondrial membrane. The structural features underlying this interaction are poorly understood. Using yeast as a model, we show that the Insert B domain of the Dnm1 guanosine triphosphatase (a DRP) contains a novel motif required for association with the mitochondrial adaptor Mdv1. Mutation of this conserved motif specifically disrupted Dnm1–Mdv1 interactions, blocking Dnm1 recruitment and mitochondrial fission. Suppressor mutations in Mdv1 that restored Dnm1–Mdv1 interactions and fission identified potential protein-binding interfaces on the Mdv1 β-propeller domain. These results define the first known function for Insert B in DRP–adaptor interactions. Based on the variability of Insert B sequences and adaptor proteins, we propose that Insert B domains and mitochondrial adaptors have coevolved to meet the unique requirements for mitochondrial fission of different organisms.
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