Novel Structure of the N Terminus in Yeast Fis1 Correlates with a Specialized Function in Mitochondrial Fission

• Published in: The Journal of biological chemistry Vol. 280; no. 22; pp. 21444 - 21452
• Main Authors: Suzuki, Motoshi, Neutzner, Albert, Tjandra, Nico, Youle, Richard J.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 03.06.2005; American Society for Biochemistry and Molecular Biology
• Subjects: Adaptor Proteins, Signal Transducing; Amino Acid Motifs; Amino Acid Sequence; Carrier Proteins - chemistry; Carrier Proteins - metabolism; Genotype; Green Fluorescent Proteins - metabolism; GTP Phosphohydrolases - chemistry; Humans; Magnetic Resonance Spectroscopy; Mitochondria - metabolism; Mitochondrial Proteins - chemistry; Mitochondrial Proteins - physiology; Models, Molecular; Molecular Sequence Data; Peptides - chemistry; Protein Conformation; Protein Folding; Protein Structure, Secondary; Protein Structure, Tertiary; Recombinant Proteins - chemistry; Saccharomyces cerevisiae; Saccharomyces cerevisiae - metabolism; Saccharomyces cerevisiae Proteins - chemistry; Saccharomyces cerevisiae Proteins - metabolism; Saccharomyces cerevisiae Proteins - physiology; Sequence Homology, Amino Acid; Subcellular Fractions
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M414092200

Mitochondrial fission is facilitated by a multiprotein complex assembled at the division site. The required components of the fission machinery in Saccharomyces cerevisiae include Dnm1, Fis1, and Mdv1. In the present study, we determined the protein structure of yeast Fis1 using NMR spectroscopy. Although the six α-helices, as well as their folding, in the yeast Fis1 structure are similar to those of the tetratricopeptide repeat (TPR) domains of the human Fis1 structure, the two structures differ in their N termini. The N-terminal tail of human Fis1 is flexible and unstructured, whereas a major segment of the longer N terminus of yeast Fis1 is fixed to the concave face formed by the six α-helices in the TPR domains. To investigate the role of the fixed N terminus, exogenous Fis1 was expressed in yeast lacking the endogenous protein. Expression of yeast Fis1 protein rescued mitochondrial fission in Δfis1 yeast only when the N-terminal TPR binding segment was left intact. The presence of this segment is also correlated to the recruitment of Mdv1 to mitochondria. The conformation of the N-terminal segment embedded in the TPR pocket indicates an intra-molecular regulation of Fis1 bioactivity. Although the TPR-like helix bundle of Fis1 mediates the interaction with Dnm1 and Mdv1, the N terminus of Fis1 is a prerequisite to recruit Mdv1 to facilitate mitochondrial fission.