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Nadia El Mammeri - One of the best experts on this subject based on the ideXlab platform.
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Structural and molecular basis of cross-seeding barriers in Amyloids
Proceedings of the National Academy of Sciences of the United States of America, 2021Co-Authors: Asen Daskalov, Nadia El Mammeri, Melanie Berbon, Benjamin Bardiaux, Denis Martinez, Virginie Coustou, Loren Andreas, Jan Stanek, Abdelmajid Noubhani, Brice KauffmannAbstract:Neurodegenerative disorders are frequently associated with β-sheet-rich Amyloid deposits. Amyloid-forming proteins can aggregate under different structural conformations known as strains, which can exhibit a prion-like behavior and distinct pathophenotypes. Precise molecular determinants defining strain specificity and cross-strain interactions (cross-seeding) are currently unknown. The HET-s prion protein from the fungus Podospora anserina represents a model system to study the fundamental properties of prion Amyloids. Here, we report the Amyloid prion structure of HELLF, a distant homolog of the model prion HET-s. We find that these two Amyloids, sharing only 17% sequence identity, have nearly identical β-solenoid folds but lack cross-seeding ability in vivo, indicating that prion specificity can differ in extremely similar Amyloid folds. We engineer the HELLF sequence to explore the limits of the sequence-to-fold conservation and to pinpoint determinants of cross-seeding and prion specificity. We find that Amyloid fold conservation occurs even at an exceedingly low level of identity to HET-s (5%). Next, we derive a HELLF-based sequence, termed HEC, able to breach the cross-seeding barrier in vivo between HELLF and HET-s, unveiling determinants controlling cross-seeding at residue level. These findings show that virtually identical Amyloid backbone structures might not be sufficient for cross-seeding and that critical side-chain positions could determine the seeding specificity of an Amyloid fold. Our work redefines the conceptual boundaries of prion strain and sheds light on key molecular features concerning an important class of pathogenic agents.
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Molecular architecture of bacterial Amyloids in Bacillus biofilms
FASEB Journal, 2019Co-Authors: Nadia El Mammeri, Jesus Hierrezuelo, James Tolchard, Jesús Cámara-almirón, Joaquín Caro-astorga, Ana Álvarez-mena, Antoine Dutour, Melanie Berbon, Jayakrishna Shenoy, Estelle MorvanAbstract:The formation of biofilms provides structural and adaptive bacterial response to the environment. In Bacillus species, the biofilm extracellular matrix is composed of exopolysaccharides, hydrophobins, and several functional Amyloid proteins. We report, using multiscale approaches such as solid-state NMR (SSNMR), electron microscopy, X-ray diffraction, dynamic light scattering, attenuated total reflection Fourier transform infrared (FTIR), and immune-gold labeling, the molecular architecture of B. subtilis and pathogenic B. cereus functional Amyloids. SSNMR data reveal that the major Amyloid component TasA in its fibrillar Amyloid form contain beta-sheet and alpha-helical secondary structure, suggesting a nontypical Amyloid architecture in B. subtilis. Proteinase K digestion experiments indicate the Amyloid moiety is 100 aa long, and subsequent SSNMR and FTIR signatures for B. subtilis and B. cereus TasA filaments highlight a conserved Amyloid fold, albeit with substantial differences in structural polymorphism and secondary structure composition. Structural analysis and coassembly data on the accessory protein TapA in B. subtilis and its counterpart camelysin in B. cereus reveal a catalyzing effect between the functional Amyloid proteins and a common structural architecture, suggesting a coassembly in the context of biofilm formation. Our findings highlight nontypical Amyloid behavior of these bacterial functional Amyloids, underlining structural variations between biofilms even in closely related bacterial species.-El Mammeri, N., Hierrezuelo, J., Tolchard, J., Camara-Almiron, J., Caro-Astorga, J., Alvarez-Mena, A., Dutour, A., Berbon, M., Shenoy, J., Morvan, E., Grelard, A., Kauffmann, B., Lecomte, S., de Vicente, A., Habenstein, B., Romero, D., Loquet, A. Molecular architecture of bacterial Amyloids in Bacillus biofilms.
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3D structure determination of Amyloid fibrils using solid-state NMR spectroscopy
Methods, 2018Co-Authors: Antoine Loquet, Nadia El Mammeri, Melanie Berbon, Stanek Jan, Benjamin Bardiaux, Guido Pintacuda, Birgit HabensteinAbstract:The Amyloid fold is structurally characterized by a typical cross-β architecture, which is under debate to represent an energy-favourable folding state that many globular or natively unfolded proteins can adopt. Being initially solely associated with Amyloid fibrils observed in the propagation of several neurodegenerative disorders, the discovery of non-pathological (or " functional ") Amyloids in many native biological processes has recently further intensified the general interest invested in those cross-β supramolecular assemblies. The insoluble and non-crystalline nature of Amyloid fibrils and their usually inhomogeneous appearance on the mesoscopic level pose a challenge to biophysical techniques aiming at an atomic-level structural characterization. Solid-state NMR spectroscopy (SSNMR) has granted breakthroughs in structural investigations on Amyloid fibrils ranging from the assessment of the impact of polymorphism in disease development to the 3D atomic structure determination of Amyloid fibrils. First landmark studies towards the characterization of atomic structures and interactions involving functional Amyloids have provided new impulses in the understanding of the role of the Amyloid fold in native biological functions. Over the last decade many strategies have been developed in protein isotope labelling, NMR resonance assignment, distance restraint determination and 3D structure calculation of Amyloid fibrils based on SSNMR approaches. We will here discuss the emerging concepts and state-of-the-art methods related to the assessment of Amyloid structures and interactions involving Amyloid entities by SSNMR.
Melanie Berbon - One of the best experts on this subject based on the ideXlab platform.
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Structural and molecular basis of cross-seeding barriers in Amyloids
Proceedings of the National Academy of Sciences of the United States of America, 2021Co-Authors: Asen Daskalov, Nadia El Mammeri, Melanie Berbon, Benjamin Bardiaux, Denis Martinez, Virginie Coustou, Loren Andreas, Jan Stanek, Abdelmajid Noubhani, Brice KauffmannAbstract:Neurodegenerative disorders are frequently associated with β-sheet-rich Amyloid deposits. Amyloid-forming proteins can aggregate under different structural conformations known as strains, which can exhibit a prion-like behavior and distinct pathophenotypes. Precise molecular determinants defining strain specificity and cross-strain interactions (cross-seeding) are currently unknown. The HET-s prion protein from the fungus Podospora anserina represents a model system to study the fundamental properties of prion Amyloids. Here, we report the Amyloid prion structure of HELLF, a distant homolog of the model prion HET-s. We find that these two Amyloids, sharing only 17% sequence identity, have nearly identical β-solenoid folds but lack cross-seeding ability in vivo, indicating that prion specificity can differ in extremely similar Amyloid folds. We engineer the HELLF sequence to explore the limits of the sequence-to-fold conservation and to pinpoint determinants of cross-seeding and prion specificity. We find that Amyloid fold conservation occurs even at an exceedingly low level of identity to HET-s (5%). Next, we derive a HELLF-based sequence, termed HEC, able to breach the cross-seeding barrier in vivo between HELLF and HET-s, unveiling determinants controlling cross-seeding at residue level. These findings show that virtually identical Amyloid backbone structures might not be sufficient for cross-seeding and that critical side-chain positions could determine the seeding specificity of an Amyloid fold. Our work redefines the conceptual boundaries of prion strain and sheds light on key molecular features concerning an important class of pathogenic agents.
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Molecular architecture of bacterial Amyloids in Bacillus biofilms
FASEB Journal, 2019Co-Authors: Nadia El Mammeri, Jesus Hierrezuelo, James Tolchard, Jesús Cámara-almirón, Joaquín Caro-astorga, Ana Álvarez-mena, Antoine Dutour, Melanie Berbon, Jayakrishna Shenoy, Estelle MorvanAbstract:The formation of biofilms provides structural and adaptive bacterial response to the environment. In Bacillus species, the biofilm extracellular matrix is composed of exopolysaccharides, hydrophobins, and several functional Amyloid proteins. We report, using multiscale approaches such as solid-state NMR (SSNMR), electron microscopy, X-ray diffraction, dynamic light scattering, attenuated total reflection Fourier transform infrared (FTIR), and immune-gold labeling, the molecular architecture of B. subtilis and pathogenic B. cereus functional Amyloids. SSNMR data reveal that the major Amyloid component TasA in its fibrillar Amyloid form contain beta-sheet and alpha-helical secondary structure, suggesting a nontypical Amyloid architecture in B. subtilis. Proteinase K digestion experiments indicate the Amyloid moiety is 100 aa long, and subsequent SSNMR and FTIR signatures for B. subtilis and B. cereus TasA filaments highlight a conserved Amyloid fold, albeit with substantial differences in structural polymorphism and secondary structure composition. Structural analysis and coassembly data on the accessory protein TapA in B. subtilis and its counterpart camelysin in B. cereus reveal a catalyzing effect between the functional Amyloid proteins and a common structural architecture, suggesting a coassembly in the context of biofilm formation. Our findings highlight nontypical Amyloid behavior of these bacterial functional Amyloids, underlining structural variations between biofilms even in closely related bacterial species.-El Mammeri, N., Hierrezuelo, J., Tolchard, J., Camara-Almiron, J., Caro-Astorga, J., Alvarez-Mena, A., Dutour, A., Berbon, M., Shenoy, J., Morvan, E., Grelard, A., Kauffmann, B., Lecomte, S., de Vicente, A., Habenstein, B., Romero, D., Loquet, A. Molecular architecture of bacterial Amyloids in Bacillus biofilms.
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3D structure determination of Amyloid fibrils using solid-state NMR spectroscopy
Methods, 2018Co-Authors: Antoine Loquet, Nadia El Mammeri, Melanie Berbon, Stanek Jan, Benjamin Bardiaux, Guido Pintacuda, Birgit HabensteinAbstract:The Amyloid fold is structurally characterized by a typical cross-β architecture, which is under debate to represent an energy-favourable folding state that many globular or natively unfolded proteins can adopt. Being initially solely associated with Amyloid fibrils observed in the propagation of several neurodegenerative disorders, the discovery of non-pathological (or " functional ") Amyloids in many native biological processes has recently further intensified the general interest invested in those cross-β supramolecular assemblies. The insoluble and non-crystalline nature of Amyloid fibrils and their usually inhomogeneous appearance on the mesoscopic level pose a challenge to biophysical techniques aiming at an atomic-level structural characterization. Solid-state NMR spectroscopy (SSNMR) has granted breakthroughs in structural investigations on Amyloid fibrils ranging from the assessment of the impact of polymorphism in disease development to the 3D atomic structure determination of Amyloid fibrils. First landmark studies towards the characterization of atomic structures and interactions involving functional Amyloids have provided new impulses in the understanding of the role of the Amyloid fold in native biological functions. Over the last decade many strategies have been developed in protein isotope labelling, NMR resonance assignment, distance restraint determination and 3D structure calculation of Amyloid fibrils based on SSNMR approaches. We will here discuss the emerging concepts and state-of-the-art methods related to the assessment of Amyloid structures and interactions involving Amyloid entities by SSNMR.
Brice Kauffmann - One of the best experts on this subject based on the ideXlab platform.
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Structural and molecular basis of cross-seeding barriers in Amyloids
Proceedings of the National Academy of Sciences of the United States of America, 2021Co-Authors: Asen Daskalov, Nadia El Mammeri, Melanie Berbon, Benjamin Bardiaux, Denis Martinez, Virginie Coustou, Loren Andreas, Jan Stanek, Abdelmajid Noubhani, Brice KauffmannAbstract:Neurodegenerative disorders are frequently associated with β-sheet-rich Amyloid deposits. Amyloid-forming proteins can aggregate under different structural conformations known as strains, which can exhibit a prion-like behavior and distinct pathophenotypes. Precise molecular determinants defining strain specificity and cross-strain interactions (cross-seeding) are currently unknown. The HET-s prion protein from the fungus Podospora anserina represents a model system to study the fundamental properties of prion Amyloids. Here, we report the Amyloid prion structure of HELLF, a distant homolog of the model prion HET-s. We find that these two Amyloids, sharing only 17% sequence identity, have nearly identical β-solenoid folds but lack cross-seeding ability in vivo, indicating that prion specificity can differ in extremely similar Amyloid folds. We engineer the HELLF sequence to explore the limits of the sequence-to-fold conservation and to pinpoint determinants of cross-seeding and prion specificity. We find that Amyloid fold conservation occurs even at an exceedingly low level of identity to HET-s (5%). Next, we derive a HELLF-based sequence, termed HEC, able to breach the cross-seeding barrier in vivo between HELLF and HET-s, unveiling determinants controlling cross-seeding at residue level. These findings show that virtually identical Amyloid backbone structures might not be sufficient for cross-seeding and that critical side-chain positions could determine the seeding specificity of an Amyloid fold. Our work redefines the conceptual boundaries of prion strain and sheds light on key molecular features concerning an important class of pathogenic agents.
Asen Daskalov - One of the best experts on this subject based on the ideXlab platform.
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Structural and molecular basis of cross-seeding barriers in Amyloids
Proceedings of the National Academy of Sciences of the United States of America, 2021Co-Authors: Asen Daskalov, Nadia El Mammeri, Melanie Berbon, Benjamin Bardiaux, Denis Martinez, Virginie Coustou, Loren Andreas, Jan Stanek, Abdelmajid Noubhani, Brice KauffmannAbstract:Neurodegenerative disorders are frequently associated with β-sheet-rich Amyloid deposits. Amyloid-forming proteins can aggregate under different structural conformations known as strains, which can exhibit a prion-like behavior and distinct pathophenotypes. Precise molecular determinants defining strain specificity and cross-strain interactions (cross-seeding) are currently unknown. The HET-s prion protein from the fungus Podospora anserina represents a model system to study the fundamental properties of prion Amyloids. Here, we report the Amyloid prion structure of HELLF, a distant homolog of the model prion HET-s. We find that these two Amyloids, sharing only 17% sequence identity, have nearly identical β-solenoid folds but lack cross-seeding ability in vivo, indicating that prion specificity can differ in extremely similar Amyloid folds. We engineer the HELLF sequence to explore the limits of the sequence-to-fold conservation and to pinpoint determinants of cross-seeding and prion specificity. We find that Amyloid fold conservation occurs even at an exceedingly low level of identity to HET-s (5%). Next, we derive a HELLF-based sequence, termed HEC, able to breach the cross-seeding barrier in vivo between HELLF and HET-s, unveiling determinants controlling cross-seeding at residue level. These findings show that virtually identical Amyloid backbone structures might not be sufficient for cross-seeding and that critical side-chain positions could determine the seeding specificity of an Amyloid fold. Our work redefines the conceptual boundaries of prion strain and sheds light on key molecular features concerning an important class of pathogenic agents.
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Theme and variations: evolutionary diversification of the HET-s functional Amyloid motif
Scientific Reports, 2015Co-Authors: Asen Daskalov, Witold Dyrka, Sven J SaupeAbstract:In mammals and fungi, Nod-like receptors (NLR) activate downstream cell death execution proteins by a prion-like mechanism. In Podospora anserina, the NWD2 NLR activates the HET-S Helo-domain pore-forming protein by converting its prion-forming domain into a characteristic β-solenoid Amyloid fold. The Amyloid forming region of HET-S/s comprises two repetitions of a 21 amino acid motif. Herein, we systematically analyze the sequences of C-terminal regions of fungal HeLo and HeLo-like domain proteins to identify HET-s-related Amyloid motifs (HRAM). We now identify four novel HRAM subfamilies in addition to the canonical HET-S/s subfamily. These novel motifs share the pseudo-repeat structure of HET-S/s and a specific pattern of distribution of hydrophobic and polar residues. Sequence co-variance analyses predict parallel in-register β-stacking of the two repeats and residue-residue interactions compatible with the β-solenoid fold. As described for HET-S, most genes encoding the HeLo proteins are adjacent to genes encoding NLRs also displaying HRAMs. The motifs of the NLRs are similar to those of their cognate HeLo-domain protein, indicating concerted evolution between repeats. This study shows that HET-s-related Amyloid motifs are more common than anticipated and that they have diversified into discrete subfamilies that apparently share a common overall fold. Amyloids are self-templating protein polymers assembled by stacking of β-strands 1. Amyloid formation is often associated with disease, in particular neurodegenerative age-related pathologies such as Alzheimer's or Parkinson's diseases or other conditions like type 2 diabetes 2,3. Amyloid formation has also been linked to cancer with a proposed role of p53 Amyloids in tumorogenesis 4. Yet, Amyloids also fulfill a range of different functions inside and outside cells 5–7. Such so-called functional Amyloids are involved in hormone and toxin storage and release, formation of cell surface structures in microorganisms and scaffolding of pigment synthesis. A role in the regulation of cell states is also described in yeast, where prion Amyloids behave as epigenetic regulatory switches 8. Recently, it has also been reported that functional Amyloids play a role in cell fate controlling sig-naling cascades both in mammals and fungi. In mammals, the RIP1 and RIP3 kinases which control the necroptosis cell death pathway form an Amyloid-like complex assembled via short conserved motifs termed RHIM (for RIP homotypic interaction motifs) 9
Benjamin Bardiaux - One of the best experts on this subject based on the ideXlab platform.
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Structural and molecular basis of cross-seeding barriers in Amyloids
Proceedings of the National Academy of Sciences of the United States of America, 2021Co-Authors: Asen Daskalov, Nadia El Mammeri, Melanie Berbon, Benjamin Bardiaux, Denis Martinez, Virginie Coustou, Loren Andreas, Jan Stanek, Abdelmajid Noubhani, Brice KauffmannAbstract:Neurodegenerative disorders are frequently associated with β-sheet-rich Amyloid deposits. Amyloid-forming proteins can aggregate under different structural conformations known as strains, which can exhibit a prion-like behavior and distinct pathophenotypes. Precise molecular determinants defining strain specificity and cross-strain interactions (cross-seeding) are currently unknown. The HET-s prion protein from the fungus Podospora anserina represents a model system to study the fundamental properties of prion Amyloids. Here, we report the Amyloid prion structure of HELLF, a distant homolog of the model prion HET-s. We find that these two Amyloids, sharing only 17% sequence identity, have nearly identical β-solenoid folds but lack cross-seeding ability in vivo, indicating that prion specificity can differ in extremely similar Amyloid folds. We engineer the HELLF sequence to explore the limits of the sequence-to-fold conservation and to pinpoint determinants of cross-seeding and prion specificity. We find that Amyloid fold conservation occurs even at an exceedingly low level of identity to HET-s (5%). Next, we derive a HELLF-based sequence, termed HEC, able to breach the cross-seeding barrier in vivo between HELLF and HET-s, unveiling determinants controlling cross-seeding at residue level. These findings show that virtually identical Amyloid backbone structures might not be sufficient for cross-seeding and that critical side-chain positions could determine the seeding specificity of an Amyloid fold. Our work redefines the conceptual boundaries of prion strain and sheds light on key molecular features concerning an important class of pathogenic agents.
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3D structure determination of Amyloid fibrils using solid-state NMR spectroscopy
Methods, 2018Co-Authors: Antoine Loquet, Nadia El Mammeri, Melanie Berbon, Stanek Jan, Benjamin Bardiaux, Guido Pintacuda, Birgit HabensteinAbstract:The Amyloid fold is structurally characterized by a typical cross-β architecture, which is under debate to represent an energy-favourable folding state that many globular or natively unfolded proteins can adopt. Being initially solely associated with Amyloid fibrils observed in the propagation of several neurodegenerative disorders, the discovery of non-pathological (or " functional ") Amyloids in many native biological processes has recently further intensified the general interest invested in those cross-β supramolecular assemblies. The insoluble and non-crystalline nature of Amyloid fibrils and their usually inhomogeneous appearance on the mesoscopic level pose a challenge to biophysical techniques aiming at an atomic-level structural characterization. Solid-state NMR spectroscopy (SSNMR) has granted breakthroughs in structural investigations on Amyloid fibrils ranging from the assessment of the impact of polymorphism in disease development to the 3D atomic structure determination of Amyloid fibrils. First landmark studies towards the characterization of atomic structures and interactions involving functional Amyloids have provided new impulses in the understanding of the role of the Amyloid fold in native biological functions. Over the last decade many strategies have been developed in protein isotope labelling, NMR resonance assignment, distance restraint determination and 3D structure calculation of Amyloid fibrils based on SSNMR approaches. We will here discuss the emerging concepts and state-of-the-art methods related to the assessment of Amyloid structures and interactions involving Amyloid entities by SSNMR.
