Mitochondrial fission is facilitated by a multi-protein 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 6 a-helices, as well as their folding, in the yeast Fis1 structure are similar to those of the 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 6 a-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 fis1 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. While 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 in order to facilitate mitochondrial fission.
|Evidence ID||Analyze ID||Interactor||Interactor Systematic Name||Interactor||Interactor Systematic Name||Type||Assay||Annotation||Action||Modification||Phenotype||Source||Reference||Note|
|Evidence ID||Analyze ID||Gene||Gene Systematic Name||Gene Ontology Term||Gene Ontology Term ID||Qualifier||Aspect||Method||Evidence||Source||Assigned On||Annotation Extension||Reference|
|Evidence ID||Analyze ID||Gene||Gene Systematic Name||Phenotype||Experiment Type||Experiment Type Category||Mutant Information||Strain Background||Chemical||Details||Reference|
|Evidence ID||Analyze ID||Regulator||Regulator Systematic Name||Target||Target Systematic Name||Experiment||Assay||Construct||Conditions||Strain Background||Reference|