6JFL

Nucleotide-free Mitofusin2 (MFN2)

Summary for 6JFL

• Entry DOI: 10.2210/pdb6jfl/pdb
• Descriptor: Mitofusin-2,cDNA FLJ57997, highly similar to Transmembrane GTPase MFN2, GLYCEROL, CALCIUM ION, ... (4 entities in total)
• Functional Keywords: mitochondriral fusion, gtpase activity, cmt2a, membrane protein
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 4
• Total formula weight: 199454.26

Authors

Li, Y.J.,Cao, Y.L.,Feng, J.X.,Qi, Y.B.,Meng, S.X.,Yang, J.F.,Zhong, Y.T.,Kang, S.S.,Chen, X.X.,Lan, L.,Luo, L.,Yu, B.,Chen, S.D.,Chan, D.C.,Hu, J.J.,Gao, S. (deposition date: 2019-02-10, release date: 2019-11-13, Last modification date: 2023-11-22)

Primary citation

Li, Y.J.,Cao, Y.L.,Feng, J.X.,Qi, Y.,Meng, S.,Yang, J.F.,Zhong, Y.T.,Kang, S.,Chen, X.,Lan, L.,Luo, L.,Yu, B.,Chen, S.,Chan, D.C.,Hu, J.,Gao, S.
Structural insights of human mitofusin-2 into mitochondrial fusion and CMT2A onset.
Nat Commun, 10:4914-4914, 2019

PubMed Abstract: Mitofusin-2 (MFN2) is a dynamin-like GTPase that plays a central role in regulating mitochondrial fusion and cell metabolism. Mutations in MFN2 cause the neurodegenerative disease Charcot-Marie-Tooth type 2A (CMT2A). The molecular basis underlying the physiological and pathological relevance of MFN2 is unclear. Here, we present crystal structures of truncated human MFN2 in different nucleotide-loading states. Unlike other dynamin superfamily members including MFN1, MFN2 forms sustained dimers even after GTP hydrolysis via the GTPase domain (G) interface, which accounts for its high membrane-tethering efficiency. The biochemical discrepancy between human MFN2 and MFN1 largely derives from a primate-only single amino acid variance. MFN2 and MFN1 can form heterodimers via the G interface in a nucleotide-dependent manner. CMT2A-related mutations, mapping to different functional zones of MFN2, lead to changes in GTP hydrolysis and homo/hetero-association ability. Our study provides fundamental insight into how mitofusins mediate mitochondrial fusion and the ways their disruptions cause disease.

PubMed: 31664033
DOI: 10.1038/s41467-019-12912-0

Experimental method

X-RAY DIFFRACTION (2.806 Å)