scholarly journals Amyloid-Like Aggregation in Diseases and Biomaterials: Osmosis of Structural Information

2021 ◽  
Vol 9 ◽  
Author(s):  
Nicole Balasco ◽  
Carlo Diaferia ◽  
Giancarlo Morelli ◽  
Luigi Vitagliano ◽  
Antonella Accardo
Keyword(s):  
Neurodegenerative Diseases ◽  
Structural Biology ◽  
Structural Characterization ◽  
Structural Information ◽  
Data Bank ◽  
Spectroscopic Properties ◽  
Structural Motif ◽  
Peptide Chemistry ◽  
Research Areas

The discovery that the polypeptide chain has a remarkable and intrinsic propensity to form amyloid-like aggregates endowed with an extraordinary stability is one of the most relevant breakthroughs of the last decades in both protein/peptide chemistry and structural biology. This observation has fundamental implications, as the formation of these assemblies is systematically associated with the insurgence of severe neurodegenerative diseases. Although the ability of proteins to form aggregates rich in cross-β structure has been highlighted by recent studies of structural biology, the determination of the underlying atomic models has required immense efforts and inventiveness. Interestingly, the progressive molecular and structural characterization of these assemblies has opened new perspectives in apparently unrelated fields. Indeed, the self-assembling through the cross-β structure has been exploited to generate innovative biomaterials endowed with promising mechanical and spectroscopic properties. Therefore, this structural motif has become the fil rouge connecting these diversified research areas. In the present review, we report a chronological recapitulation, also performing a survey of the structural content of the Protein Data Bank, of the milestones achieved over the years in the characterization of cross-β assemblies involved in the insurgence of neurodegenerative diseases. A particular emphasis is given to the very recent successful elucidation of amyloid-like aggregates characterized by remarkable molecular and structural complexities. We also review the state of the art of the structural characterization of cross-β based biomaterials by highlighting the benefits of the osmosis of information between these two research areas. Finally, we underline the new promising perspectives that recent successful characterizations of disease-related amyloid-like assemblies can open in the biomaterial field.

scholarly journals Extracting structural information of Au colloids at ultra-dilute concentrations: identification of growth during nanoparticle immobilization

2019 ◽  
Vol 1 (7) ◽  
pp. 2546-2552 ◽  
Author(s):  
George F. Tierney ◽  
Donato Decarolis ◽  
Norli Abdullah ◽  
Scott M. Rogers ◽  
Shusaku Hayama ◽  
...  
Keyword(s):  
Absorption Spectroscopy ◽  
Structural Characterization ◽  
Structural Information ◽  
Particle Growth ◽  
Au Nanoparticle ◽  
X Ray ◽  
Colloidal Au ◽  
X Ray Absorption ◽  
Au Colloids

This paper describes the structural characterization of ultra-dilute colloidal Au nanoparticle solutions using X-ray absorption spectroscopy (XAS) and the particle growth during immobilization.

Uncovering the structures of modular polyketide synthases

2015 ◽  
Vol 32 (3) ◽  
pp. 436-453 ◽  
Author(s):  
Kira J. Weissman
Keyword(s):  
Electron Microscopy ◽  
Structural Biology ◽  
Structural Characterization ◽  
Small Angle ◽  
Single Particle ◽  
Polyketide Synthases ◽  
X Ray ◽  
X Ray Scattering ◽  
Cryo Electron Microscopy

This review covers a breakthrough in the structural biology of the gigantic modular polyketide synthases (PKS): the structural characterization of intact modules by single-particle cryo-electron microscopy and small-angle X-ray scattering.

scholarly journals Studying the Structures of Relaxed and Fuzzy Interactions: The Diverse World of S100 Complexes

2021 ◽  
Vol 8 ◽  
Author(s):  
Péter Ecsédi ◽  
Gergő Gógl ◽  
László Nyitray
Keyword(s):  
Neurodegenerative Diseases ◽  
Structural Biology ◽  
Binding Proteins ◽  
Structural Information ◽  
Protein Complexes ◽  
Point Of View ◽  
S100 Proteins ◽  
Current State ◽  
Diverse World

S100 proteins are small, dimeric, Ca2+-binding proteins of considerable interest due to their associations with cancer and rheumatic and neurodegenerative diseases. They control the functions of numerous proteins by forming protein–protein complexes with them. Several of these complexes were found to display “fuzzy” properties. Examining these highly flexible interactions, however, is a difficult task, especially from a structural biology point of view. Here, we summarize the available in vitro techniques that can be deployed to obtain structural information about these dynamic complexes. We also review the current state of knowledge about the structures of S100 complexes, focusing on their often-asymmetric nature.

Structural Characterization of Ordered Phases in Hydrocarbon Dendrimers

1994 ◽  
Vol 351 ◽  
Author(s):  
Christopher J. Buchko ◽  
Atisa Sioshansi ◽  
Zhifu Xu ◽  
Jeffrey S. Moore ◽  
David C. Martin
Keyword(s):  
Structural Characterization ◽  
Rational Design ◽  
Structural Information ◽  
Molecular Architecture ◽  
Thermal Transitions ◽  
Self Assembling ◽  
Transmission Electron ◽  
Ordered Phases ◽  
Construction Of Self

ABSTRACTStructural characterization of phenylacetylene dendrimers (PADs) makes it possible to explore the relationship between molecular architecture and condensed phase organization. The size and geometry of the PAD series is precisely controlled, with phenylacetylene units emanating from a central phenylene in the manner of a tridendron. The branched molecule rapidly increases in size with each synthetic generation. The “shape-persistent” nature of the phenylacetylene molecule makes it ideal for use in the construction of self-assembling supramolecular systems.Transmission electron microscopy (TEM) has been used to identify the crystal structure of lower generation PADs, and wide-angle X-ray studies confirm the decrease in crystallinity with size. Hot stage optical microscopy studies of thermal transitions reveal melting points for lower generation PADs, and an apparent glass transition for the amorphous higher generations. This type of structural information is essential to the rational design of self-assembling materials.

scholarly journals Structural Characterization of the Essential Cell Division Protein FtsE and Its Interaction with FtsX in Streptococcus pneumoniae

mBio ◽  
2020 ◽  
Vol 11 (5) ◽  
Author(s):  
Martin Alcorlo ◽  
Daniel Straume ◽  
Joe Lutkenhaus ◽  
Leiv Sigve Håvarstein ◽  
Juan A. Hermoso
Keyword(s):  
Cell Wall ◽  
Cell Division ◽  
Streptococcus Pneumoniae ◽  
Structural Characterization ◽  
Bound States ◽  
Structural Information ◽  
Structural Plasticity ◽  
Membrane Complex

ABSTRACT FtsEX is a membrane complex widely conserved across diverse bacterial genera and involved in critical processes such as recruitment of division proteins and in spatial and temporal regulation of muralytic activity during cell division or sporulation. FtsEX is a member of the ABC transporter superfamily. The component FtsX is an integral membrane protein, whereas FtsE is an ATPase and is required for the transmission of a conformational signal from the cytosol through the membrane to regulate the activity of cell wall hydrolases in the periplasm. Both proteins are essential in the major human respiratory pathogenic bacterium Streptococcus pneumoniae, and FtsX interacts with the modular peptidoglycan hydrolase PcsB at the septum. Here, we report high-resolution structures of pneumococcal FtsE bound to different nucleotides. Structural analysis revealed that FtsE contains all the conserved structural motifs associated with ATPase activity and afforded interpretation of the in vivo dimeric arrangement in both the ADP and ATP states. Interestingly, three specific FtsE regions with high structural plasticity were identified that shape the cavity in which the cytosolic region of FtsX would be inserted. The residues corresponding to the FtsX coupling helix, responsible for contacting FtsE, were identified and validated by in vivo mutagenesis studies showing that this interaction is essential for cell growth and proper morphology. IMPORTANCE Bacterial cell division is a central process that requires exquisite orchestration of both the cell wall biosynthetic and lytic machineries. The essential membrane complex FtsEX, widely conserved across bacteria, plays a central role by recruiting proteins to the divisome apparatus and by regulating periplasmic muralytic activity from the cytosol. FtsEX is a member of the type VII family of the ABC-superfamily, but instead of being a transporter, it couples the ATP hydrolysis catalyzed by FtsE to mechanically transduce a conformational signal that provokes the activation of peptidoglycan (PG) hydrolases. So far, no structural information is available for FtsE. Here, we provide the structural characterization of FtsE, confirming its ATPase nature and revealing regions with high structural plasticity which are key for FtsE binding to FtsX. The complementary binding region in FtsX has also been identified and validated in vivo. Our results provide evidence on how the difference between the ATP/ADP-bound states in FtsE would dramatically alter the interaction of FtsEX with the PG hydrolase PcsB in pneumococcal division.

scholarly journals Structural characterization of the essential cell division protein FtsE and its interaction with FtsX in Streptococcus pneumoniae

2020 ◽  
Author(s):  
Martin Alcorlo ◽  
Daniel Straume ◽  
Joe Lutkenhaus ◽  
Leiv Sigve Håvarstein ◽  
Juan A. Hermoso
Keyword(s):  
Cell Wall ◽  
Cell Division ◽  
Streptococcus Pneumoniae ◽  
Structural Characterization ◽  
Structural Information ◽  
Structural Plasticity ◽  
Central Process ◽  
Membrane Complex

ABSTRACTFtsEX is a membrane complex widely conserved across diverse bacterial genera and involved in critical processes such as recruitment of division proteins and in spatial and temporal regulation of muralytic activity during cell division or sporulation. FtsEX is a member of the ABC transporter superfamily, where FtsX is an integral membrane protein and FtsE is an ATPase, required for mechanotransmission of the signal from the cytosol through the membrane, to regulate the activity of cell-wall hydrolases in the periplasm. Both proteins are essential in the major human respiratory pathogenic bacterium, Streptococcus pneumoniae and interact with the modular peptidoglycan hydrolase PcsB at the septum. Here, we report the high-resolution structures of pneumococcal FtsE in complex with different nucleotides. Structural analysis reveals that FtsE contains all the conserved structural motifs associated with ATPase activity, and allowed interpretation of the in vivo dimeric arrangement in both ADP and ATP states. Interestingly, three specific FtsE regions were identified with high structural plasticity that shape the cavity in which the cytosolic region of FtsX would be inserted. The residues corresponding to the FtsX coupling helix, responsible for FtsE contact, were identified and validated by in vivo mutagenesis studies showing that this interaction is essential for cell growth and proper morphology.IMPORTANCEBacterial cell division is a central process that requires exquisite orchestration of both the cell wall biosynthetic and lytic machineries. The essential membrane complex FtsEX, widely conserved across bacteria, play a central role by recruiting proteins to the divisome apparatus and by regulating periplasmic muralytic activity from the cytosol. FtsEX is a member of the Type VII family of the ABC-superfamily but instead transporter, couple ATP hydrolysis by FtsE to mechanically transduce a conformational signal to activate PG hydrolases. So far, no structural information is available for FtsE. Here we provide the structural characterization of FtsE confirming its ATPase nature and revealing regions with high structural plasticity key for FtsX binding. The complementary region in FtsX has been also identified and validated in vivo. Our results provide evidences on how difference between ATP and ADP states in FtsE would dramatically alter FtsEX interaction with PG hydrolase PcsB in pneumococcal division.

scholarly journals Purification and Structural Characterization of Aggregation-Prone Human TDP-43 Involved in Neurodegenerative Diseases

iScience ◽  
2020 ◽  
Vol 23 (6) ◽  
pp. 101159 ◽  
Author(s):  
Gareth S.A. Wright ◽  
Tatiana F. Watanabe ◽  
Kangsa Amporndanai ◽  
Steven S. Plotkin ◽  
Neil R. Cashman ◽  
...  
Keyword(s):  
Neurodegenerative Diseases ◽  
Structural Characterization

New ultrastructural findings about Borrelia burgdorferi by cryofixation, negative staining, thin sectioning and scanning techniques

1990 ◽  
Vol 48 (3) ◽  
pp. 582-583
Author(s):  
S. F. Hayes ◽  
M. D. Corwin ◽  
T. G. Schwan ◽  
D. W. Dorward ◽  
W. Burgdorfer
Keyword(s):  
Lyme Disease ◽  
Borrelia Burgdorferi ◽  
Structural Characterization ◽  
Negative Staining ◽  
Low Speed ◽  
Thin Sectioning ◽  
Ultrastructural Findings

Characterization of Borrelia burgdorferi strains by means of negative staining EM has become an integral part of many studies related to the biology of the Lyme disease organism. However, relying solely upon negative staining to compare new isolates with prototype B31 or other borreliae is often unsatisfactory. To obtain more satisfactory results, we have relied upon a correlative approach encompassing a variety EM techniques, i.e., scanning for topographical features and cryotomy, negative staining and thin sectioning to provide a more complete structural characterization of B. burgdorferi.For characterization, isolates of B. burgdorferi were cultured in BSK II media from which they were removed by low speed centrifugation. The sedimented borrelia were carefully resuspended in stabilizing buffer so as to preserve their features for scanning and negative staining. Alternatively, others were prepared for conventional thin sectioning and for cryotomy using modified procedures. For thin sectioning, the fixative described by Ito, et al.

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