A novel motif in the yeast mitochondrial dynamin Dnm1 is essential for adaptor binding and membrane recruitment

J Cell Biol. 2012 Nov 12;199(4):613-22. doi: 10.1083/jcb.201207079.

Abstract

To initiate mitochondrial fission, dynamin-related proteins (DRPs) must bind specific adaptors on the outer mitochondrial membrane. The structural features underlying this interaction are poorly understood. Using yeast as a model, we show that the Insert B domain of the Dnm1 guanosine triphosphatase (a DRP) contains a novel motif required for association with the mitochondrial adaptor Mdv1. Mutation of this conserved motif specifically disrupted Dnm1-Mdv1 interactions, blocking Dnm1 recruitment and mitochondrial fission. Suppressor mutations in Mdv1 that restored Dnm1-Mdv1 interactions and fission identified potential protein-binding interfaces on the Mdv1 β-propeller domain. These results define the first known function for Insert B in DRP-adaptor interactions. Based on the variability of Insert B sequences and adaptor proteins, we propose that Insert B domains and mitochondrial adaptors have coevolved to meet the unique requirements for mitochondrial fission of different organisms.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adaptor Proteins, Signal Transducing / chemistry
  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / metabolism*
  • Amino Acid Motifs
  • Amino Acid Sequence
  • GTP Phosphohydrolases / chemistry*
  • GTP Phosphohydrolases / genetics
  • GTP Phosphohydrolases / metabolism*
  • Mitochondrial Membranes / metabolism*
  • Mitochondrial Proteins / chemistry*
  • Mitochondrial Proteins / genetics
  • Mitochondrial Proteins / metabolism*
  • Models, Molecular
  • Molecular Sequence Data
  • Mutation
  • Saccharomyces cerevisiae / chemistry
  • Saccharomyces cerevisiae / cytology*
  • Saccharomyces cerevisiae / metabolism*
  • Saccharomyces cerevisiae Proteins / chemistry*
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism*
  • Sequence Alignment

Substances

  • Adaptor Proteins, Signal Transducing
  • MDV1 protein, S cerevisiae
  • Mitochondrial Proteins
  • Saccharomyces cerevisiae Proteins
  • GTP Phosphohydrolases
  • DNM1 protein, S cerevisiae