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Crystal structure of Mdm12 reveals the architecture and dynamic organization of the ERMES complex

Hanbin Jeong1,2, Jumi Park1,2, Changwook Lee3,2,4

  • 1Department of Biological Sciences, School of Life Sciences Ulsan National Institute of Science and Technology, Ulsan, Korea.

EMBO Reports
|November 9, 2016
PubMed

Insights

The crystal structure of yeast Mdm12 reveals its SMP domain organization and a phospholipid-binding site. This finding advances understanding of the endoplasmic reticulum-mitochondria encounter structure (ERMES) complex assembly.

Area of Science:

  • Cell biology
  • Structural biology
  • Biochemistry

Background:

  • The endoplasmic reticulum-mitochondria encounter structure (ERMES) complex tethers ER and mitochondria membranes.
  • ERMES is crucial for cellular function and is composed of Mdm10, Mdm12, Mmm1, and Mdm34.
  • Mdm12, Mmm1, and Mdm34 share a common SMP domain.

Purpose of the Study:

  • To determine the crystal structure of Saccharomyces cerevisiae Mdm12.
  • To elucidate the structural organization and phospholipid-binding properties of Mdm12 within the ERMES complex.

Main Methods:

  • X-ray crystallography was used to determine the crystal structure of S. cerevisiae Mdm12.
  • Biochemical experiments were conducted to identify phospholipid-binding sites and preferences.

Main Results:

  • Mdm12 forms a dimeric SMP structure via β1-strand domain swapping.
  • A phospholipid-binding site was identified within a hydrophobic channel, with a potential preference for glycerophospholipids with positive head groups.
  • Both full-length and truncated Mdm12 (lacking residues 74-114) showed similar asymmetric unit organization, forming tetramers and hexamers, respectively.

Conclusions:

  • The Mdm12 structure provides novel insights into SMP domain organization within the ERMES complex.
  • Mdm12 interacts with Mdm34 via head-to-head SMP domain contact.
  • Mdm12 interacts with Mmm1 via tail-to-tail SMP domain contact.
Keywords:
ERMES complexMdm12SMP domaincrystal structurephospholipid binding

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