Crystal structure of Mdm12 reveals the architecture and dynamic organization of the ERMES complex.
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.
Department of Biological Sciences, School of Life Sciences Ulsan National Institute of Science and Technology, Ulsan, Korea.|Cell Logistics Research Center, Gwangju Institute of Science and Technology, Gwangju, Korea.
Hanbin
0000-0002-3878-1813
H
Jeong
Department of Biological Sciences, School of Life Sciences Ulsan National Institute of Science and Technology, Ulsan, Korea.|Cell Logistics Research Center, Gwangju Institute of Science and Technology, Gwangju, Korea.
Jumi
J
Park
Department of Biological Sciences, School of Life Sciences Ulsan National Institute of Science and Technology, Ulsan, Korea changwook@unist.ac.kr.|Cell Logistics Research Center, Gwangju Institute of Science and Technology, Gwangju, Korea.|Center for Genome Integrity, Institute for Basic Science (IBS), Ulsan, Korea.
Changwook
0000-0002-3016-9478
C
Lee
D001665:Binding Sites; D018360:Crystallography, X-Ray; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D008565:Membrane Proteins / Q000737:chemistry* / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism*; D063154:Mitochondrial Dynamics; D051336:Mitochondrial Membranes / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000737:chemistry* / Q000378:metabolism; D008958:Models, Molecular; D010743:Phospholipids / Q000378:metabolism; D000072417:Protein Domains; D012441:Saccharomyces cerevisiae / Q000737:chemistry / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry* / Q000378:metabolism
C543343:Mdm12 protein, S cerevisiae; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D010743:Phospholipids; D029701:Saccharomyces cerevisiae Proteins
ERMES complex; Mdm12; SMP domain; crystal structure; phospholipid binding