Membrane promotes tBID interaction with BCLXL

García‐Sáez, Ana J.; Ries, Jonas; Orzáez, Mar; Pérez‐Payá, Enrique; Schwille, Petra

doi:10.1038/nsmb.1671

Cited by 120 publications

(157 citation statements)

References 52 publications

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“…Furthermore, Arf and Sar GTPases release an N-terminal helix upon GTP binding that inserts into the membrane and induces membrane remodeling (39,40). The amphipathic helix α7 might also interact with binding partners of GIMAPs, e.g., Bcl2 family members, which are known to associate with each other via amphipathic helices that bind into a hydrophobic acceptor groove (41), and this interaction is strongly promoted in the presence of membranes (42). The C interface of GIMAPs is unique leading to a different architecture of the oligomer compared to septins (25) and dynamin/MxA (33).…”

Section: Discussionmentioning

confidence: 99%

Structural basis of oligomerization in septin-like GTPase of immunity-associated protein 2 (GIMAP2)

Schwefel

Fröhlich²,

Eichhorst³

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

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GTPases of immunity-associated proteins (GIMAPs) are a distinctive family of GTPases, which control apoptosis in lymphocytes and play a central role in lymphocyte maturation and lymphocyte-associated diseases. To explore their function and mechanism, we determined crystal structures of a representative member, GIMAP2, in different nucleotide-loading and oligomerization states. Nucleotide-free and GDP-bound GIMAP2 were monomeric and revealed a guanine nucleotide-binding domain of the TRAFAC (translation factor associated) class with a unique amphipathic helix α7 packing against switch II. In the absence of α7 and the presence of GTP, GIMAP2 oligomerized via two distinct interfaces in the crystal. GTP-induced stabilization of switch I mediates dimerization across the nucleotide-binding site, which also involves the GIMAP specificity motif and the nucleotide base. Structural rearrangements in switch II appear to induce the release of α7 allowing oligomerization to proceed via a second interface. The unique architecture of the linear oligomer was confirmed by mutagenesis. Furthermore, we showed a function for the GIMAP2 oligomer at the surface of lipid droplets. Although earlier studies indicated that GIMAPs are related to the septins, the current structure also revealed a strikingly similar nucleotide coordination and dimerization mode as in the dynamin GTPase. Based on this, we reexamined the relationships of the septin-and dynamin-like GTPases and demonstrate that these are likely to have emerged from a common membrane-associated dimerizing ancestor. This ancestral property appears to be critical for the role of GIMAPs as nucleotide-regulated scaffolds on intracellular membranes. G protein | protein structure

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Section: Discussionmentioning

confidence: 99%

Structural basis of oligomerization in septin-like GTPase of immunity-associated protein 2 (GIMAP2)

Schwefel

Fröhlich²,

Eichhorst³

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

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“…The C terminus of BCL-XL contains a clear MOM-targeting motif and shares sequence homology with those of BAX, BAK and other MOM-targeted BCL-2 proteins. The lipid bilayer membrane strongly influences BCL-2 protein-protein interactions, 20,48,84,106 and several lines of evidence show that the hydrophobic C terminus of BCL-XL is important for regulating both the interaction of BCL-XL with its partners and its membrane integration. However, most structural studies have focused on truncated forms of BCL-XL lacking the hydrophobic C terminus, to promote solubility, and little is known about how BCL-XL interacts with the membrane or with membrane-associated BAX and BID.…”

Section: How Does Bcl-xl Protect Against Cell Death?mentioning

confidence: 99%

The rheostat in the membrane: BCL-2 family proteins and apoptosis

et al. 2013

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Apoptosis, a mechanism for programmed cell death, has key roles in human health and disease. Many signals for cellular life and death are regulated by the BCL-2 family proteins and converge at mitochondria, where cell fate is ultimately decided. The BCL-2 family includes both pro-life (e.g. BCL-XL) and pro-death (e.g. BAX, BAK) proteins. Previously, it was thought that a balance between these opposing proteins, like a simple 'rheostat', could control the sensitivity of cells to apoptotic stresses. Later, this rheostat concept had to be extended, when it became clear that BCL-2 family proteins regulate each other through a complex network of bimolecular interactions, some transient and some relatively stable. Now, studies have shown that the apoptotic circuitry is even more sophisticated, in that BCL-2 family interactions are spatially dynamic, even in nonapoptotic cells. For example, BAX and BCL-XL can shuttle between the cytoplasm and the mitochondrial outer membrane (MOM). Upstream signaling pathways can regulate the cytoplasmic-MOM equilibrium of BAX and thereby adjust the sensitivity of cells to apoptotic stimuli. Thus, we can view the MOM as the central locale of a dynamic life-death rheostat. BAX invariably forms extensive homo-oligomers after activation in membranes. However, recent studies, showing that activated BAX monomers determine the kinetics of MOM permeabilization (MOMP), perturb the lipid bilayer and form nanometer size pores, pose questions about the role of the oligomerization. Other lingering questions concern the molecular mechanisms of BAX redistribution between MOM and cytoplasm and the details of BAX/BAK-membrane assemblies. Future studies need to delineate how BCL-2 family proteins regulate MOMP, in concert with auxiliary MOM proteins, in a dynamic membrane environment. Technologies aimed at elucidating the structure and function of the full-length proteins in membranes are needed to illuminate some of these critical issues.

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“…Photon detection was done with the avalanche photodiodes of the ConFocor 3 module, and the photon arrival times were recorded in the photon mode of the hardware correlator Flex 02-01D/C. Measurements were done as described previously (34). Briefly, the detection volume was repeatedly scanned perpendicularly through the equator of a GUV in a frame mode with Nx2 pixels to scan the two parallel lines.…”

Section: Quantification Of Pi(45)p 2 -Dependent Fgf2 Oligomerizationmentioning

confidence: 99%

“…Briefly, the detection volume was repeatedly scanned perpendicularly through the equator of a GUV in a frame mode with Nx2 pixels to scan the two parallel lines. Data analysis was performed with software written in MATLAB (34). The photon stream was binned in 2-s bins and arranged as a matrix, with every row corresponding to one line scan.…”

Section: Quantification Of Pi(45)p 2 -Dependent Fgf2 Oligomerizationmentioning

confidence: 99%

Phosphatidylinositol 4,5-Bisphosphate (PI(4,5)P2)-dependent Oligomerization of Fibroblast Growth Factor 2 (FGF2) Triggers the Formation of a Lipidic Membrane Pore Implicated in Unconventional Secretion

Steringer

Bleicken

Andreas

et al. 2012

Journal of Biological Chemistry

103

181

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Background: PI(4,5)P 2 -and tyrosine phosphorylation-dependent unconventional secretion of FGF2 is mediated by direct translocation across the plasma membrane. Results: PI(4,5)P 2 -mediated membrane recruitment causes oligomerization of tyrosine-phosphorylated FGF2 that, in turn, triggers the formation of a lipidic membrane pore. Conclusion: Membrane-inserted FGF2 oligomers represent intermediates of membrane translocation during unconventional secretion. Significance: Mechanistic insight into a novel self-sustained mechanism of protein translocation across membranes is provided.

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Membrane promotes tBID interaction with BCLXL

Cited by 120 publications

References 52 publications

Structural basis of oligomerization in septin-like GTPase of immunity-associated protein 2 (GIMAP2)

Structural basis of oligomerization in septin-like GTPase of immunity-associated protein 2 (GIMAP2)

The rheostat in the membrane: BCL-2 family proteins and apoptosis

Phosphatidylinositol 4,5-Bisphosphate (PI(4,5)P2)-dependent Oligomerization of Fibroblast Growth Factor 2 (FGF2) Triggers the Formation of a Lipidic Membrane Pore Implicated in Unconventional Secretion

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