The structural basis for membrane binding and pore formation by lymphocyte perforin

Nature ◽  
2010 ◽  
Vol 468 (7322) ◽  
pp. 447-451 ◽  
Author(s):  
Ruby H. P. Law ◽  
Natalya Lukoyanova ◽  
Ilia Voskoboinik ◽  
Tom T. Caradoc-Davies ◽  
Katherine Baran ◽  
...  
Keyword(s):  
Pore Formation ◽  
Membrane Binding ◽  
Structural Basis

scholarly journals Dual modes of membrane binding direct pore formation by Streptolysin O

2015 ◽  
Vol 97 (6) ◽  
pp. 1036-1050 ◽  
Author(s):  
Cara C. Mozola ◽  
Michael G. Caparon
Keyword(s):  
Pore Formation ◽  
Membrane Binding ◽  
Streptolysin O

scholarly journals Coordinated autoinhibition of F-BAR domain membrane binding and WASp activation by Nervous Wreck

2016 ◽  
Vol 113 (38) ◽  
pp. E5552-E5561 ◽  
Author(s):  
Tatiana B. Stanishneva-Konovalova ◽  
Charlotte F. Kelley ◽  
Tania L. Eskin ◽  
Emily M. Messelaar ◽  
Steven A. Wasserman ◽  
...  
Keyword(s):  
Bound States ◽  
Membrane Binding ◽  
Structural Basis ◽  
Synaptic Growth ◽  
Sh3 Domains ◽  
Actin Organization ◽  
Bar Domain ◽  
Src Homology

Membrane remodeling by Fes/Cip4 homology-Bin/Amphiphysin/Rvs167 (F-BAR) proteins is regulated by autoinhibitory interactions between their SRC homology 3 (SH3) and F-BAR domains. The structural basis of autoregulation, and whether it affects interactions of SH3 domains with other cellular ligands, remain unclear. Here we used single-particle electron microscopy to determine the structure of the F-BAR protein Nervous Wreck (Nwk) in both soluble and membrane-bound states. On membrane binding, Nwk SH3 domains do not completely dissociate from the F-BAR dimer, but instead shift from its concave surface to positions on either side of the dimer. Unexpectedly, along with controlling membrane binding, these autoregulatory interactions inhibit the ability of Nwk-SH3a to activate Wiskott–Aldrich syndrome protein (WASp)/actin related protein (Arp) 2/3-dependent actin filament assembly. In Drosophila neurons, Nwk autoregulation restricts SH3a domain-dependent synaptopod formation, synaptic growth, and actin organization. Our results define structural rearrangements in Nwk that control F-BAR–membrane interactions as well as SH3 domain activities, and suggest that these two functions are tightly coordinated in vitro and in vivo.

scholarly journals Bax-type Apoptotic Proteins Porate Pure Lipid Bilayers through a Mechanism Sensitive to Intrinsic Monolayer Curvature

2002 ◽  
Vol 277 (51) ◽  
pp. 49360-49365 ◽  
Author(s):  
Gorka Basañez ◽  
Juanita C. Sharpe ◽  
Jennifer Galanis ◽  
Teresa B. Brandt ◽  
J. Marie Hardwick ◽  
...  
Keyword(s):  
Lipid Bilayers ◽  
Mitochondrial Membrane ◽  
Pore Formation ◽  
Membrane Binding ◽  
Membrane Permeabilization ◽  
Outer Mitochondrial Membrane ◽  
Intrinsic Curvature ◽  
Differential Effects ◽  
Cleavage Fragment ◽  
Induced Changes

During apoptosis, Bax-type proteins permeabilize the outer mitochondrial membrane to release intermembrane apoptogenic factors into the cytosol via a poorly understood mechanism. We have proposed that Bax and ΔN76Bcl-xL(the Bax-like cleavage fragment of Bcl-xL) function by forming pores that are at least partially composed of lipids (lipidic pore formation). Since the membrane monolayer must bend during lipidic pore formation, we here explore the effect of intrinsic membrane monolayer curvature on pore formation. Nonlamellar lipids with positive intrinsic curvature such as lysophospholipids promoted membrane permeabilization, whereas nonlamellar lipids with negative intrinsic curvature such as diacylglycerol and phosphatidylethanolamine inhibited membrane permeabilization. The differential effects of nonlamellar lipids on membrane permeabilization were not correlated with lipid-induced changes in membrane binding or insertion of Bax or ΔN76Bcl-xL. Altogether, these results are consistent with a model whereby Bax-type proteins change the bending propensity of the membrane to form pores comprised at least in part of lipids in a structure of net positive monolayer curvature.

scholarly journals Model for the architecture of caveolae based on a flexible, net-like assembly of Cavin1 and Caveolin discs

2016 ◽  
Vol 113 (50) ◽  
pp. E8069-E8078 ◽  
Author(s):  
Miriam Stoeber ◽  
Pascale Schellenberger ◽  
C. Alistair Siebert ◽  
Cedric Leyrat ◽  
Ari Helenius ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Complex Formation ◽  
Membrane Binding ◽  
Coiled Coil ◽  
Structural Basis ◽  
Membrane Domains ◽  
Coiled Coil Domain ◽  
Regular Dodecahedron ◽  
Plasma Membrane Domains ◽  
Electron Cryotomography

Caveolae are invaginated plasma membrane domains involved in mechanosensing, signaling, endocytosis, and membrane homeostasis. Oligomers of membrane-embedded caveolins and peripherally attached cavins form the caveolar coat whose structure has remained elusive. Here, purified Cavin1 60S complexes were analyzed structurally in solution and after liposome reconstitution by electron cryotomography. Cavin1 adopted a flexible, net-like protein mesh able to form polyhedral lattices on phosphatidylserine-containing vesicles. Mutating the two coiled-coil domains in Cavin1 revealed that they mediate distinct assembly steps during 60S complex formation. The organization of the cavin coat corresponded to a polyhedral nano-net held together by coiled-coil segments. Positive residues around the C-terminal coiled-coil domain were required for membrane binding. Purified caveolin 8S oligomers assumed disc-shaped arrangements of sizes that are consistent with the discs occupying the faces in the caveolar polyhedra. Polygonal caveolar membrane profiles were revealed in tomograms of native caveolae inside cells. We propose a model with a regular dodecahedron as structural basis for the caveolae architecture.

scholarly journals Structural basis of membrane recognition of Toxoplasma gondii vacuole by Irgb6

2021 ◽  
Vol 5 (1) ◽  
pp. e202101149
Author(s):  
Yumiko Saijo-Hamano ◽  
Aalaa Alrahman Sherif ◽  
Ariel Pradipta ◽  
Miwa Sasai ◽  
Naoki Sakai ◽  
...  
Keyword(s):  
Toxoplasma Gondii ◽  
Conformational Changes ◽  
Molecular Mechanisms ◽  
Structural Information ◽  
Parasitophorous Vacuole ◽  
Membrane Binding ◽  
Structural Basis ◽  
In Silico Docking ◽  
Binding Interface ◽  
Dimerization Interface

The p47 immunity-related GTPase (IRG) Irgb6 plays a pioneering role in host defense against Toxoplasma gondii infection. Irgb6 is recruited to the parasitophorous vacuole membrane (PVM) formed by T. gondii and disrupts it. Despite the importance of this process, the molecular mechanisms accounting for PVM recognition by Irgb6 remain elusive because of lack of structural information on Irgb6. Here we report the crystal structures of mouse Irgb6 in the GTP-bound and nucleotide-free forms. Irgb6 exhibits a similar overall architecture to other IRGs in which GTP binding induces conformational changes in both the dimerization interface and the membrane-binding interface. The membrane-binding interface of Irgb6 assumes a unique conformation, composed of N- and C-terminal helical regions forming a phospholipid binding site. In silico docking of phospholipids further revealed membrane-binding residues that were validated through mutagenesis and cell-based assays. Collectively, these data demonstrate a novel structural basis for Irgb6 to recognize T. gondii PVM in a manner distinct from other IRGs.

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