Crystal structure of Mdm12 reveals the architecture and dynamic organization of the
            <scp>ERMES</scp>
            complex

Jeong, Hanbin; Park, Jumi; Lee, Chang-Wook

doi:10.15252/embr.201642706

Cited by 68 publications

(134 citation statements)

References 40 publications

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“…The TULIP domain of E-Syt2 binds glycerolipids preferentially to sterol by a factor of up to 5:1 13, 15. While E-Syt2 shows little or no headgroup specificity, Mdm12 shows considerable specificity for cationic headgroups [16], possibly because of binding to the acidic side chain D255, found only in Mdm12 [14].…”

Section: Redrawing the Picture Of Lipid Trafficmentioning

confidence: 99%

Advances on the Transfer of Lipids by Lipid Transfer Proteins

Wong¹,

Čopič

Levine³

2017

Trends in Biochemical Sciences

167

161

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Transfer of lipid across the cytoplasm is an essential process for intracellular lipid traffic. Lipid transfer proteins (LTPs) are defined by highly controlled in vitro experiments. The functional relevance of these is supported by evidence for the same reactions inside cells. Major advances in the LTP field have come from structural bioinformatics identifying new LTPs, and from the development of countercurrent models for LTPs. However, the ultimate aim is to unite in vitro and in vivo data, and this is where much progress remains to be made. Even where in vitro and in vivo experiments align, rates of transfer tend not to match. Here we set out some of the advances that might test how LTPs work.

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Section: Redrawing the Picture Of Lipid Trafficmentioning

confidence: 99%

Advances on the Transfer of Lipids by Lipid Transfer Proteins

Wong¹,

Čopič

Levine³

2017

Trends in Biochemical Sciences

167

161

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“…In addition to head-to-head dimerisation (as in Fig. 2E) there is a tail-to-tail self-interaction [32]. Here the helix in element 6 of one monomer forms contacts (white “ladders”) with residues in both the inserted loops of a second monomer (highlighted in light blue); B: Heterotetramers of Mdm12 (grey) and Mmm1 (green) form an extended structure with a central bend of 45°; redrawn from single particle EM visualisations by AhYoung et al [41].…”

Section: Structure-function Relationships Among the Tulipsmentioning

confidence: 94%

“…The prediction that SMP domains are homologous to TULIPs such as CETP/BPI has since been verified by crystal structures of three SMP domains [31], [32], [33]. SMP domains had been identified throughout eukaryotic evolution in moderately large numbers per genome (human 7, yeast 7, plant 11), with various accessory domains also present [34].…”

Section: Classifying the Full Range Of Tulipsmentioning

confidence: 96%

“…Even if this interface is physiologically important for Mdm12 self-interaction, it is unlikely to apply to Mmm1, because this lacks the key contacting residues and the inserts found in Mdm12. This means that the molecular basis by which a Mdm12-Mmm1 heterotetramer could form is still unknown [32].

Fig. 4Multimerisation of SMP domains in ERMES.…”

Section: Structure-function Relationships Among the Tulipsmentioning

confidence: 99%

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Tubular lipid binding proteins (TULIPs) growing everywhere

Wong¹,

Levine²

2017

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research

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Tubular lipid binding proteins (TULIPs) have become a focus of interest in the cell biology of lipid signalling, lipid traffic and membrane contact sites. Each tubular domain has an internal pocket with a hydrophobic lining that can bind a hydrophobic molecule such as a lipid. This allows TULIP proteins to carry lipids through the aqueous phase. TULIP domains were first found in a large family of extracellular proteins related to the bacterial permeability-inducing protein (BPI) and cholesterol ester transfer protein (CETP). Since then, the same fold and lipid transfer capacity have been found in SMP domains (so-called for their occurrence in synaptotagmin, mitochondrial and lipid binding proteins), which localise to intracellular membrane contact sites. Here the methods for identifying known TULIPs are described, and used to find previously unreported TULIPs, one in the silk polymer and another in prokaryotes illustrated by the E. coli protein YceB. The bacterial TULIP alters views on the likely evolution of the domain, suggesting its presence in the last universal common ancestor. The major function of TULIPs is to handle lipids, but we still do not know how they work in detail, or how many more remain to be discovered. This article is part of a Special Issue entitled: Membrane Contact Sites edited by Christian Ungermann and Benoit Kornmann.

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“…Data were processed in XDS [20]. The structure of Mdm12 was solved by molecular replacement with Phaser [21] using the Sce-Mmd12 crystal structures described by Jeong et al [22] (PDB accession codes 5GYD and 5GYK) as search probes. To minimize model bias, the search model consisted in the monomer where the 14 first residues, corresponding to the swapped N-terminal β-strand S1 and the connecting loop preceding helix H1 were removed; two copies of Sce -Mdm12 were located in the asymmetric unit.…”

Section: Methodsmentioning

confidence: 99%

Crystal structure of Mdm12 and combinatorial reconstitution of Mdm12/Mmm1 ERMES complexes for structural studies

AhYoung

Cascio³

et al. 2017

Biochemical and Biophysical Research Communications

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Membrane contact sites between organelles serve as molecular hubs for the exchange of metabolites and signals. In yeast, the Endoplasmic Reticulum − Mitochondrion Encounter Structure (ERMES) tethers these two organelles likely to facilitate the non-vesicular exchange of essential phospholipids. Present in Fungi and Amoebas but not in Metazoans, ERMES is composed of five distinct subunits; among those, Mdm12, Mmm1 and Mdm34 each contain an SMP domain functioning as a lipid transfer module. We previously showed that the SMP domains of Mdm12 and Mmm1 form a hetero-tetramer. Here we describe our strategy to diversify the number of Mdm12/Mmm1 complexes suited for structural studies. We use sequence analysis of orthologues combined to protein engineering of disordered regions to guide the design of protein constructs and expand the repertoire of Mdm12/Mmm1 complexes more likely to crystallize. Using this combinatorial approach we report crystals of Mdm12/Mmm1 ERMES complexes currently diffracting to 4.5 Å resolution and a new structure of Mdm12 solved at 4.1 Å resolution. Our structure reveals a monomeric form of Mdm12 with a conformationally dynamic N-terminal β-strand; it differs from a previously reported homodimeric structure where the N-terminal β strands where swapped to promote dimerization. Based on our electron microscopy data, we propose a refined pseudo-atomic model of the Mdm12/Mmm1 complex that agrees with our crystallographic and small-angle X-ray scattering (SAXS) solution data.

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

Cited by 68 publications

References 40 publications

Advances on the Transfer of Lipids by Lipid Transfer Proteins

Advances on the Transfer of Lipids by Lipid Transfer Proteins

Tubular lipid binding proteins (TULIPs) growing everywhere

Crystal structure of Mdm12 and combinatorial reconstitution of Mdm12/Mmm1 ERMES complexes for structural studies

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