scholarly journals C-terminal juxtamembrane region of full-length M2 protein forms a membrane surface associated amphipathic helix

2015 ◽  
Vol 24 (3) ◽  
pp. 426-429 ◽  
Author(s):  
Shenstone Huang ◽  
Bryan Green ◽  
Megan Thompson ◽  
Richard Chen ◽  
Jessica Thomaston ◽  
...  
Keyword(s):  
Membrane Surface ◽  
Full Length ◽  
Amphipathic Helix ◽  
M2 Protein ◽  
Juxtamembrane Region

scholarly journals Conformational analysis of the full-length M2 protein of the influenza A virus using solid-state NMR

2013 ◽  
Vol 22 (11) ◽  
pp. 1623-1638 ◽  
Author(s):  
Shu Yu Liao ◽  
Keith J. Fritzsching ◽  
Mei Hong
Keyword(s):  
Solid State ◽  
Conformational Analysis ◽  
Influenza A Virus ◽  
Solid State Nmr ◽  
Influenza A ◽  
Full Length ◽  
M2 Protein

scholarly journals Structural Influences: Cholesterol, Drug, and Proton Binding to Full-Length Influenza A M2 Protein

2016 ◽  
Vol 110 (6) ◽  
pp. 1391-1399 ◽  
Author(s):  
E. Vindana Ekanayake ◽  
Riqiang Fu ◽  
Timothy A. Cross
Keyword(s):  
Influenza A ◽  
Full Length ◽  
M2 Protein ◽  
Proton Binding

scholarly journals Structure of a lipid A phosphoethanolamine transferase suggests how conformational changes govern substrate binding

2017 ◽  
Vol 114 (9) ◽  
pp. 2218-2223 ◽  
Author(s):  
Anandhi Anandan ◽  
Genevieve L. Evans ◽  
Karmen Condic-Jurkic ◽  
Megan L. O’Mara ◽  
Constance M. John ◽  
...  
Keyword(s):  
Conformational Changes ◽  
Bacterial Infections ◽  
Lipid A ◽  
Substrate Binding ◽  
Membrane Surface ◽  
Limited Proteolysis ◽  
Multidrug Resistant ◽  
Full Length ◽  
Rational Drug Design ◽  
Cationic Antimicrobial Peptide

Multidrug-resistant (MDR) gram-negative bacteria have increased the prevalence of fatal sepsis in modern times. Colistin is a cationic antimicrobial peptide (CAMP) antibiotic that permeabilizes the bacterial outer membrane (OM) and has been used to treat these infections. The OM outer leaflet is comprised of endotoxin containing lipid A, which can be modified to increase resistance to CAMPs and prevent clearance by the innate immune response. One type of lipid A modification involves the addition of phosphoethanolamine to the 1 and 4′ headgroup positions by phosphoethanolamine transferases. Previous structural work on a truncated form of this enzyme suggested that the full-length protein was required for correct lipid substrate binding and catalysis. We now report the crystal structure of a full-length lipid A phosphoethanolamine transferase from Neisseria meningitidis, determined to 2.75-Å resolution. The structure reveals a previously uncharacterized helical membrane domain and a periplasmic facing soluble domain. The domains are linked by a helix that runs along the membrane surface interacting with the phospholipid head groups. Two helices located in a periplasmic loop between two transmembrane helices contain conserved charged residues and are implicated in substrate binding. Intrinsic fluorescence, limited proteolysis, and molecular dynamics studies suggest the protein may sample different conformational states to enable the binding of two very different- sized lipid substrates. These results provide insights into the mechanism of endotoxin modification and will aid a structure-guided rational drug design approach to treating multidrug-resistant bacterial infections.

scholarly journals Structure and mechanism of TRAPPIII-mediated Rab1 activation

2020 ◽  
Author(s):  
Aaron M.N. Joiner ◽  
Ben P. Phillips ◽  
Kumar Yugandhar ◽  
Ethan J. Sanford ◽  
Marcus B. Smolka ◽  
...  
Keyword(s):  
Secretory Pathway ◽  
Membrane Surface ◽  
Regulatory Subunit ◽  
Amphipathic Helix ◽  
Nucleotide Exchange ◽  
Early Secretory Pathway ◽  
Guanine Nucleotide Exchange ◽  
Nucleotide Exchange Factor ◽  
Α Helix ◽  
And Function

ABSTRACTThe GTPase Rab1 is a master regulator of both the early secretory pathway and autophagy. Rab1 activation is controlled by its GEF (guanine nucleotide exchange factor), the multi-subunit TRAPPIII complex. The Trs85 regulatory subunit is critical for robust activation of Rab1 but its mechanistic role within the complex has remained unclear. Here we report the cryo-EM structure of the intact yeast TRAPPIII complex bound to its substrate Rab1/Ypt1. The orientation of the Rab1/Ypt1 hypervariable domain when bound to the complex leads to a model for how TRAPPIII associates with and activates Rab1/Ypt1 at the membrane surface. We identify a conserved amphipathic α-helix motif within Trs85 and demonstrate that this helix is required for stable membrane binding and Rab1/Ypt1 activation by TRAPPIII. Taken together, our results provide a comprehensive analysis of the structure and function of the yeast TRAPPIII complex and reveal that the key function of Trs85 is to serve as a membrane anchor, via its amphipathic helix, for the entire TRAPPIII complex.

scholarly journals Structure of Yeast Sulfhydryl Oxidase Erv1 Reveals Electron Transfer of the Disulfide Relay System in the Mitochondrial Intermembrane Space

2012 ◽  
Vol 287 (42) ◽  
pp. 34961-34969 ◽  
Author(s):  
Peng-Chao Guo ◽  
Jin-Di Ma ◽  
Yong-Liang Jiang ◽  
Shu-Jie Wang ◽  
Zhang-Zhi Bao ◽  
...  
Keyword(s):  
Electron Transfer ◽  
Electron Donor ◽  
Full Length ◽  
Intermembrane Space ◽  
Amphipathic Helix ◽  
Sulfhydryl Oxidase ◽  
Relay System ◽  
Helix Bundle ◽  
Mitochondrial Intermembrane Space ◽  
Four Helix Bundle

The disulfide relay system in the mitochondrial intermembrane space drives the import of proteins with twin CX9C or twin CX3C motifs by an oxidative folding mechanism. This process requires disulfide bond transfer from oxidized Mia40 to a substrate protein. Reduced Mia40 is reoxidized/regenerated by the FAD-linked sulfhydryl oxidase Erv1 (EC 1.8.3.2). Full-length Erv1 consists of a flexible N-terminal shuttle domain (NTD) and a conserved C-terminal core domain (CTD). Here, we present crystal structures at 2.0 Å resolution of the CTD and at 3.0 Å resolution of a C30S/C133S double mutant of full-length Erv1 (Erv1FL). Similar to previous homologous structures, the CTD exists as a homodimer, with each subunit consisting of a conserved four-helix bundle that accommodates the isoalloxazine ring of FAD and an additional single-turn helix. The structure of Erv1FL enabled us to identify, for the first time, the three-dimensional structure of the Erv1NTD, which is an amphipathic helix flanked by two flexible loops. This structure also represents an intermediate state of electron transfer from the NTD to the CTD of another subunit. Comparative structural analysis revealed that the four-helix bundle of the CTD forms a wide platform for the electron donor NTD. Moreover, computational simulation combined with multiple-sequence alignment suggested that the amphipathic helix close to the shuttle redox enter is critical for the recognition of Mia40, the upstream electron donor. These findings provide structural insights into electron transfer from Mia40 via the shuttle domain of one subunit of Erv1 to the CTD of another Erv1 subunit.

Isotropic Bicelles Stabilize the Juxtamembrane Region of the Influenza M2 Protein for Solution NMR Studies

Biochemistry ◽  
2013 ◽  
Vol 52 (47) ◽  
pp. 8420-8429 ◽  
Author(s):  
Jolyon K. Claridge ◽  
Jussi Aittoniemi ◽  
Daniel M. Cooper ◽  
Jason R. Schnell
Keyword(s):  
Solution Nmr ◽  
M2 Protein ◽  
Nmr Studies ◽  
Juxtamembrane Region

scholarly journals Short and Spaced Twisted Tapes to Mitigate Fouling in Tubular Membranes

2019 ◽  
Author(s):  
Matthias Wessling
Keyword(s):  
Shear Rate ◽  
Pressure Drop ◽  
Membrane Fouling ◽  
Membrane Surface ◽  
Full Length ◽  
Twisted Tape ◽  
Static Mixers ◽  
Fouling Mitigation ◽  
Twisted Tapes ◽  
3D Printed

Static mixers are an efficient means to mitigate membrane fouling as they deflect the fluid, thus increasing the shear rate at the membrane surface and enhancing back-transport of rejected matter. However, inserting static mixers in the flow channel of a membrane imposes an additional pressure drop. To decrease this detrimental effect of static mixers, we shorten twisted tape mixers and investigate how this shortening translates into a reduction of fouling mitigation. We follow two approaches known from heat transfer enhancement: i) shorten the total length of the twisted tape and ii) use regularly spaced short twisted tape elements which are kept at their position by smooth rods placed in between the twisted elements. Computational fluid dynamics (CFD) is applied to analyze the flow pattern, the shear rate at the membrane and the resulting pressure drop. The results allow for the selection of modified twisted tape mixers with lower pressure loss, but sufficient flow properties for fouling mitigation. The most promising mixer designs were selected according to the CFD study, 3D-printed, and their fouling mitigation effect experimentally investigated using silica suspensions. Additionally, the effect of foulant concentration in this system is analyzed. For low silica concentrations (0.03 g/L) the short and spaced twisted tapes mitigate fouling as efficiently as the full-length twisted tape. At high silica concentrations and fluxes, the full-length mixer mitigates fouling more strongly than the short and spaced twisted tapes. However, the modified twisted tapes prove to be more energy-efficient up to a certain fouling exposure.

scholarly journals Pro-apoptotic Bid induces membrane perturbation by inserting selected lysolipids into the bilayer

2005 ◽  
Vol 387 (1) ◽  
pp. 109-118 ◽  
Author(s):  
Alexander GOONESINGHE ◽  
Elizabeth S. MUNDY ◽  
Melanie SMITH ◽  
Roya KHOSRAVI-FAR ◽  
Jean-Claude MARTINOU ◽  
...  
Keyword(s):  
Cell Death ◽  
Membrane Surface ◽  
Death Receptor ◽  
Mitochondrial Pathway ◽  
Full Length ◽  
Membrane Perturbation ◽  
C Terminus ◽  
Biochemical Level

Bid is a BH3-only member of the Bcl-2 family that regulates cell death at the level of mitochondrial membranes. Bid appears to link the mitochondrial pathway with the death receptor-mediated pathway of cell death. It is generally assumed that the f.l. (full-length) protein becomes activated after proteolytic cleavage, especially by apical caspases like caspase 8. The cleaved protein then relocates to mitochondria and promotes membrane permeabilization, presumably by interaction with mitochondrial lipids and other Bcl-2 proteins that facilitate the release of apoptogenic proteins like cytochrome c. Although the major action may reside in the C-terminus part, tBid (cleaved Bid), un-cleaved Bid also has pro-apoptotic potential when ectopically expressed in cells or in vitro. This pro-apoptotic action of f.l. Bid has remained unexplained, especially at the biochemical level. In the present study, we show that f.l. (full-length) Bid can insert specific lysolipids into the membrane surface, thereby priming mitochondria for the release of apoptogenic factors. This is most effective for lysophosphatidylcholine species that we report to accumulate in mitochondria during apoptosis induction. A Bid mutant that is not pro-apoptotic in vivo is defective in lysophosphatidylcholine-mediated membrane perturbation in vitro. Our results thus provide a biochemical explanation for the pro-apoptotic action of f.l. Bid.

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