scholarly journals A Nanoscale Model System for the Human Myelin Sheath

2021 ◽  
Author(s):  
Matthias Hoffmann ◽  
David Haselberger ◽  
Tommy Hofmann ◽  
Lisa Müller ◽  
Kevin Janson ◽  
...  
Keyword(s):  
Basic Protein ◽  
Model System ◽  
Myelin Proteins ◽  
Membrane Systems ◽  
Lipid Interactions ◽  
Functional Studies ◽  
Complex Lipid ◽  
Central Nervous Systems ◽  
Lipid Environment ◽  
First Time

Here, we for the first time establish nanodiscs with the challenging lipid composition of myelin of the peripheral or central nervous systems, respectively (PNS and CNS, both containing >40% cholesterol, which so far has been thought to be detrimental for nanodisc formation).Thus, we prove that more complex lipid model membrane systems are in general accessible through nanodiscs and can study protein-lipid interactions in myelin and factors driving myelin formation or degradation using combinations of myelin proteins in a highly controlled lipid environment resembling myelin’s cytoplasmic leaflet. For the functional studies, initial proof-of-principle experiments using myelin basic protein have been performed. <br>

scholarly journals A Nanoscale Model System for the Human Myelin Sheath

2021 ◽  
Author(s):  
Matthias Hoffmann ◽  
David Haselberger ◽  
Tommy Hofmann ◽  
Lisa Müller ◽  
Kevin Janson ◽  
...  
Keyword(s):  
Basic Protein ◽  
Model System ◽  
Myelin Proteins ◽  
Membrane Systems ◽  
Lipid Interactions ◽  
Functional Studies ◽  
Complex Lipid ◽  
Central Nervous Systems ◽  
Lipid Environment ◽  
First Time

Here, we for the first time establish nanodiscs with the challenging lipid composition of myelin of the peripheral or central nervous systems, respectively (PNS and CNS, both containing >40% cholesterol, which so far has been thought to be detrimental for nanodisc formation).Thus, we prove that more complex lipid model membrane systems are in general accessible through nanodiscs and can study protein-lipid interactions in myelin and factors driving myelin formation or degradation using combinations of myelin proteins in a highly controlled lipid environment resembling myelin’s cytoplasmic leaflet. For the functional studies, initial proof-of-principle experiments using myelin basic protein have been performed. <br>

scholarly journals A Nanoscale Model System for the Human Myelin Sheath

2021 ◽  
Author(s):  
Matthias Hoffmann ◽  
David Haselberger ◽  
Tommy Hofmann ◽  
Lisa Müller ◽  
Kevin Janson ◽  
...  
Keyword(s):  
Basic Protein ◽  
Model System ◽  
Myelin Proteins ◽  
Membrane Systems ◽  
Lipid Interactions ◽  
Functional Studies ◽  
Complex Lipid ◽  
Central Nervous Systems ◽  
Lipid Environment ◽  
First Time

Here, we for the first time establish nanodiscs with the challenging lipid composition of myelin of the peripheral or central nervous systems, respectively (PNS and CNS, both containing >40% cholesterol, which so far has been thought to be detrimental for nanodisc formation).Thus, we prove that more complex lipid model membrane systems are in general accessible through nanodiscs and can study protein-lipid interactions in myelin and factors driving myelin formation or degradation using combinations of myelin proteins in a highly controlled lipid environment resembling myelin’s cytoplasmic leaflet. For the functional studies, initial proof-of-principle experiments using myelin basic protein have been performed. <br>

scholarly journals Structural and functional studies of Arabidopsis thaliana legumain beta reveal isoform specific mechanisms of activation and substrate recognition

2020 ◽  
Vol 295 (37) ◽  
pp. 13047-13064 ◽  
Author(s):  
Elfriede Dall ◽  
Florian B. Zauner ◽  
Wai Tuck Soh ◽  
Fatih Demir ◽  
Sven O. Dahms ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Arabidopsis Thaliana ◽  
Cyclic Peptides ◽  
Molecular Mechanisms ◽  
Functional Studies ◽  
Plant Characteristic ◽  
Activation Mechanisms ◽  
Binding Pockets ◽  
First Time ◽  
Autocatalytic Activation

The vacuolar cysteine protease legumain plays important functions in seed maturation and plant programmed cell death. Because of their dual protease and ligase activity, plant legumains have become of particular biotechnological interest, e.g. for the synthesis of cyclic peptides for drug design or for protein engineering. However, the molecular mechanisms behind their dual protease and ligase activities are still poorly understood, limiting their applications. Here, we present the crystal structure of Arabidopsis thaliana legumain isoform β (AtLEGβ) in its zymogen state. Combining structural and biochemical experiments, we show for the first time that plant legumains encode distinct, isoform-specific activation mechanisms. Whereas the autocatalytic activation of isoform γ (AtLEGγ) is controlled by the latency-conferring dimer state, the activation of the monomeric AtLEGβ is concentration independent. Additionally, in AtLEGβ the plant-characteristic two-chain intermediate state is stabilized by hydrophobic rather than ionic interactions, as in AtLEGγ, resulting in significantly different pH stability profiles. The crystal structure of AtLEGβ revealed unrestricted nonprime substrate binding pockets, consistent with the broad substrate specificity, as determined by degradomic assays. Further to its protease activity, we show that AtLEGβ exhibits a true peptide ligase activity. Whereas cleavage-dependent transpeptidase activity has been reported for other plant legumains, AtLEGβ is the first example of a plant legumain capable of linking free termini. The discovery of these isoform-specific differences will allow us to identify and rationally design efficient ligases with application in biotechnology and drug development.

scholarly journals Interactions of a Bacterial Cu(I)-ATPase with a Complex Lipid Environment

Biochemistry ◽  
2018 ◽  
Vol 57 (28) ◽  
pp. 4063-4073 ◽  
Author(s):  
Henriette E. Autzen ◽  
Heidi Koldsø ◽  
Phillip J. Stansfeld ◽  
Pontus Gourdon ◽  
Mark S. P. Sansom ◽  
...  
Keyword(s):  
Complex Lipid ◽  
Lipid Environment

Ependymal explants from the lateral ventricle of the adult bovine brain: a model system for morphological and functional studies of the ependyma

2000 ◽  
Vol 300 (1) ◽  
pp. 11-19 ◽  
Author(s):  
M. Pérez-Martín ◽  
J.M. Grondona ◽  
M. Cifuentes ◽  
J.M. Pérez-Fígares ◽  
J.A. Jiménez ◽  
...  
Keyword(s):  
Lateral Ventricle ◽  
Bovine Brain ◽  
Model System ◽  
Functional Studies

scholarly journals Crystallization of the human tetraspanin protein CD9

2019 ◽  
Vol 75 (4) ◽  
pp. 254-259 ◽  
Author(s):  
Rie Umeda ◽  
Tomohiro Nishizawa ◽  
Osamu Nureki
Keyword(s):  
Variable Region ◽  
Extracellular Loop ◽  
Functional Studies ◽  
Physiological Processes ◽  
Wide Range ◽  
Membrane Spanning ◽  
Cell Migration And Proliferation ◽  
First Time ◽  
Representative Member ◽  
Tetraspanin Family

The tetraspanin family of proteins with four membrane-spanning proteins function in a wide range of physiological processes in higher organisms, including cell migration and proliferation, cell fusion, fertilization and virus infection. Although the recently reported structure of CD81 unveiled the basic architecture of this family for the first time, further structural and functional studies are required in order to understand the mechanistic details of the complicated functions of the tetraspanin-family proteins. In this study, attempts were made to crystallize human CD9, a representative member of the tetraspanin family, and it was demonstrated that the truncation of a variable region in the second long extracellular loop significantly improved crystal growth.

scholarly journals Isolation of the Ascobolus immersus spore color gene b2 and study in single cells of gene silencing by methylation induced premeiotically.

Genetics ◽  
1995 ◽  
Vol 141 (4) ◽  
pp. 1299-1314
Author(s):  
V Colot ◽  
J L Rossignol
Keyword(s):  
Gene Silencing ◽  
Physical Mapping ◽  
Meiotic Recombination ◽  
Hot Spot ◽  
Single Cells ◽  
Model System ◽  
Ascobolus Immersus ◽  
First Time ◽  
Mutant Rescue ◽  
Color Gene

Abstract The ascomycete Ascobolus immersus has been extensively used as a model system for the genetic study of meiotic recombination. More recently, an epigenetic process, known as methylation induced premeiotically (MIP), that acts on duplicated sequences has been discovered in A. immersus and has raised a new interest in this fungus. To try and extend these studies, we have now cloned the A. immersus spore color gene b2, a well characterized recombination hot-spot. Isolation of the whole gene was verified by physical mapping of four large b2 alterations, followed by transformation and mutant rescue of a null b2 allele. Transformation was also used to duplicate b2 and subject it to MIP. As a result, we were able for the first time to observe gene silencing as early as just after meiosis and in single cells. Furthermore, we have found evidence for a modulating effect of MIP on b2 expression, depending on the region of the gene that is duplicated and hence subjected to MIP.

scholarly journals The Amyloid Structure of Mouse RIPK3 (Receptor Interacting Protein Kinase 3) in Cell Necroptosis

2020 ◽  
Author(s):  
Xia-lian Wu ◽  
Hong Hu ◽  
Xing-qi Dong ◽  
Jing Zhang ◽  
Jian Wang ◽  
...  
Keyword(s):  
Structural Transformation ◽  
Self Assembly ◽  
Structural Integrity ◽  
Immune Defense ◽  
Dynamics Simulation ◽  
Amyloid Formation ◽  
Interacting Protein ◽  
Functional Studies ◽  
First Time ◽  
Human And Mouse

ABSTRACTRIPK3 amyloid complex plays crucial roles in execution of TNF-induced necroptosis and in response to immune defense in both human and mouse. We have structurally characterized the mouse RIPK3 homogeneous self-assembly using solid-state NMR, illustrating a well-ordered N-shaped amyloid core structure featured with 3 parallel in-register β-sheets. The structure is different from previously published human RIPK1/RIPK3 hetero-amyloid complex. Functional studies indicate both RIPK1-RIPK3 binding and RIPK3 amyloid formation are essential but not sufficient for RIPK3-mediated necroptosis. The structural integrity of RIPK3 fibril with three β-strands is necessary for the signaling. Molecular dynamics simulation of the mouse RIPK1/RIPK3 model indicates less stable for the hetero-amyloid to adopt RIPK3 fibril conformation, suggesting a structural transformation of RIPK3 from RIPK1-RIPK3 binding to RIPK3 amyloid formation. This structural transformation is revealed for the first time, providing a missing link connecting RIPK1-RIPK3 binding to RIPK3 homo-oligomer formation in the signal transduction.

scholarly journals High temperature gas extrusion of reactive powder mixture Ni + AL

2019 ◽  
Vol 489 (4) ◽  
pp. 358-361
Author(s):  
F. F. Galiev ◽  
I. V. Saikov ◽  
V. D. Berbentcev ◽  
A. V. Guliyutin ◽  
V. I. Bugakov ◽  
...  
Keyword(s):  
High Temperature ◽  
Powder Mixture ◽  
Model System ◽  
Steel Shell ◽  
Powder Mixtures ◽  
Reactive Powder ◽  
First Time ◽  
High Temperature Gas

The results of the study of intermetallic rods in a steel shell obtained by high-temperature gas extrusion for the first time used for reactive powder mixtures are presented. Tests were conducted on the basis of model system Ni-Al.

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