Crystal structure of Mdm12 reveals the architecture and dynamic organization of the ERMES complex.
EMBO Rep
; 17(12): 1857-1871, 2016 12.
Article
em En
| MEDLINE
| ID: mdl-27821511
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 ß1-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.
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Base de dados:
MEDLINE
Assunto principal:
Modelos Moleculares
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Proteínas de Saccharomyces cerevisiae
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Proteínas Mitocondriais
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Retículo Endoplasmático
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Dinâmica Mitocondrial
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Proteínas de Membrana
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Mitocôndrias
Idioma:
En
Revista:
EMBO Rep
Assunto da revista:
BIOLOGIA MOLECULAR
Ano de publicação:
2016
Tipo de documento:
Article