2. Academic Validation
  3. Structures of human mitofusin 1 provide insight into mitochondrial tethering

Structures of human mitofusin 1 provide insight into mitochondrial tethering

  • J Cell Biol. 2016 Dec 5;215(5):621-629. doi: 10.1083/jcb.201609019.
Yuanbo Qi 1 2,  Liming Yan 3,  Caiting Yu 3,  Xiangyang Guo 1 2,  Xin Zhou 1 2,  Xiaoyu Hu 1 2,  Xiaofang Huang 1 2,  Zihe Rao 4 5,  Zhiyong Lou 4,  Junjie Hu 6
Affiliations

Affiliations

  • 1 Department of Genetics and Cell Biology, College of Life Sciences, Nankai University, Tianjin 300071, China.
  • 2 Tianjin Key Laboratory of Protein Sciences, Nankai University, Tianjin 300071, China.
  • 3 School of Medicine, Tsinghua University, Beijing 100084, China.
  • 4 School of Medicine, Tsinghua University, Beijing 100084, China huj@ibp.ac.cn louzy@mail.tsinghua.edu.cn raozh@xtal.tsinghua.edu.cn.
  • 5 National Laboratory of Macromolecules, Institute of Biophysics, Chinese Academy of Science, Beijing 100101, China.
  • 6 National Laboratory of Macromolecules, Institute of Biophysics, Chinese Academy of Science, Beijing 100101, China huj@ibp.ac.cn louzy@mail.tsinghua.edu.cn raozh@xtal.tsinghua.edu.cn.
PMID: 27920125 DOI: 10.1083/jcb.201609019
Abstract

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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