Structures of human mitofusin 1 provide insight into mitochondrial tethering

نویسندگان

  • Yuanbo Qi
  • Liming Yan
  • Caiting Yu
  • Xiangyang Guo
  • Xin Zhou
  • Xiaoyu Hu
  • Xiaofang Huang
  • Zihe Rao
  • Zhiyong Lou
  • Junjie Hu
چکیده

Mitochondria undergo fusion and fission. The merging of outer mitochondrial membranes requires mitofusin (MFN), a dynamin-like GTPase. How exactly MFN mediates membrane fusion is poorly understood. Here, we determined crystal structures of a minimal GTPase domain (MGD) of human MFN1, including the predicted GTPase and the distal part of the C-terminal tail (CT). The structures revealed that a helix bundle (HB) formed by three helices extending from the GTPase and one extending from the CT closely attaches to the GTPase domain, resembling the configuration of bacterial dynamin-like protein. We show that the nucleotide-binding pocket is shallow and narrow, rendering weak hydrolysis and less dependence on magnesium ion, and that association of HB affects GTPase activity. MFN1 forms a dimer when GTP or GDP/BeF3-, but not GDP or other analogs, is added. In addition, clustering of vesicles containing membrane-anchored MGD requires continuous GTP hydrolysis. These results suggest that MFN tethers apposing membranes, likely through nucleotide-dependent dimerization.

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عنوان ژورنال:

دوره 215  شماره 

صفحات  -

تاریخ انتشار 2016