5YEW

Structural basis for GTP hydrolysis and conformational change of mitofusin 1 in mediating mitochondrial fusion

Summary for 5YEW

• Entry DOI: 10.2210/pdb5yew/pdb
• Descriptor: Mitofusin-1,Mitofusin-1 fusion protein, GUANOSINE-5'-DIPHOSPHATE, BERYLLIUM TRIFLUORIDE ION, ... (6 entities in total)
• Functional Keywords: mitochondria, fusion, mfn1, hydrolase
• Biological source: Homo sapiens (Human); More
• Cellular location: Mitochondrion outer membrane ; Multi- pass membrane protein . Isoform 2: Cytoplasm : Q8IWA4 Q8IWA4
• Total number of polymer chains: 3
• Total formula weight: 143909.49

Authors

Yan, L.,Qi, Y.,Huang, X.,Yu, C. (deposition date: 2017-09-20, release date: 2018-01-31, Last modification date: 2024-10-30)

Primary citation

Yan, L.,Qi, Y.,Huang, X.,Yu, C.,Lan, L.,Guo, X.,Rao, Z.,Hu, J.,Lou, Z.
Structural basis for GTP hydrolysis and conformational change of MFN1 in mediating membrane fusion
Nat. Struct. Mol. Biol., 25:233-243, 2018

PubMed Abstract: Fusion of the outer mitochondrial membrane is mediated by the dynamin-like GTPase mitofusin (MFN). Here, we determined the structure of the minimal GTPase domain (MGD) of human MFN1 in complex with GDP-BeF. The MGD folds into a canonical GTPase fold with an associating four-helix bundle, HB1, and forms a dimer. A potassium ion in the catalytic core engages GDP and BeF (GDP-BeF). Enzymatic analysis has confirmed that efficient GTP hydrolysis by MFN1 requires potassium. Compared to previously reported MGD structures, the HB1 structure undergoes a major conformational change relative to the GTPase domains, as they move from pointing in opposite directions to point in the same direction, suggesting that a swing of the four-helix bundle can pull tethered membranes closer to achieve fusion. The proposed model is supported by results from in vitro biochemical assays and mitochondria morphology rescue assays in MFN1-deleted cells. These findings offer an explanation for how Charcot-Marie-Tooth neuropathy type 2 A (CMT2A)-causing mutations compromise MFN-mediated fusion.

PubMed: 29483649
DOI: 10.1038/s41594-018-0034-8

Experimental method

X-RAY DIFFRACTION (3.2 Å)