Download MendeleyCrystal structure of Mdm12 reveals the architecture and dynamic organization of the ERMES complex
Jeong, H., Park, J., Lee, C.(2016) EMBO Rep 17: 1857-1871
- PubMed: 27821511
- DOI: https://doi.org/10.15252/embr.201642706
- Primary Citation of Related Structures:
5GYD, 5GYK - PubMed Abstract:
The endoplasmic reticulum-mitochondria encounter structure (ERMES) is a protein complex that plays a tethering role in physically connecting ER and mitochondria membranes. The ERMES complex is composed of Mdm12, Mmm1, and Mdm34, which have a SMP domain in common, and Mdm10. Here, we report the crystal structure of S. cerevisiae Mdm12. The Mdm12 forms a dimeric SMP structure through domain swapping of the β1-strand comprising residues 1-7. Biochemical experiments reveal a phospholipid-binding site located along a hydrophobic channel of the Mdm12 structure and that Mdm12 might have a binding preference for glycerophospholipids harboring a positively charged head group. Strikingly, both full-length Mdm12 and Mdm12 truncated to exclude the disordered region (residues 74-114) display the same organization in the asymmetric unit, although they crystallize as a tetramer and hexamer, respectively. Taken together, these studies provide a novel understanding of the overall organization of SMP domains in the ERMES complex, indicating that Mdm12 interacts with Mdm34 through head-to-head contact, and with Mmm1 through tail-to-tail contact of SMP domains.
Organizational Affiliation:
Department of Biological Sciences, School of Life Sciences Ulsan National Institute of Science and Technology, Ulsan, Korea.
