첨부 '1' |
---|
author | Hugh I. Kim |
---|---|
journal | Chemical Science, 2016, DOI 10.1039c6sc00153j |
Homepage | https://sites.google.com/site/hughkimgroup/ |
Amyloidosis is a clinical disorder implicated with the formation of toxic amyloid aggregates. Despite their pathological significance, it is challenging to define the structural characteristics of amyloid oligomers owing to their metastable nature. Herein, we report structural and mechanistic investigations of human islet amyloid polypeptide (hIAPP) oligomers, found in type II diabetes mellitus, in both the absence and presence of disease-relevant metal ions [i.e., Cu(II) and Zn(II)]. These metal ions show suppressive effects on hIAPP fibrillation and facilitate the generation of toxic oligomers. Using circular dichroism spectroscopy, transmission electron microscopy, gel electrophoresis, small-angle X-ray scattering, and ion mobility-mass spectrometry, we investigated the assembly mechanisms of hIAPP oligomers in the presence and absence of metal ions. Oligomerization of both metal-free hIAPP and metal-associated hIAPP monomers is initiated following a similar growth model. However, in the presence of Cu(II), hIAPP monomers self-assemble into small globular aggregates (Rg ∼ 45 Å) with a random coil structure. This Cu(II)-associated hIAPP oligomer shows an off-pathway aggregation, and is suggested to be an end product which is toxic to pancreatic β-cells. On the other hand, metal-free hIAPP and Zn(II)-associated hIAPP monomers generate relatively less toxic aggregates that eventually grow into fibrils. We suggest that the coordination of hIAPP to Cu(II) and the relatively high stability (Ka, ca. 108 M−1) of hIAPP–Cu(II) complexes result in the abnormal conformation and toxicity of hIAPP oligomers. Overall, through combining multiple biophysical methods, our studies suggest that molecular interactions between hIAPP and Cu(II) induce a different pathway for hIAPP assembly. This work will advance our knowledge of the conformational basis, assembly mechanism, and toxicity of small soluble amyloid oligomers.
http://pubs.rsc.org/en/content/articlelanding/2016/sc/c6sc00153j#!divAbstract
-
(Semi)ladder-Type Bithiophene Imide-Based All-Acceptor Semiconductors: Synthesis, Structure–Property Correlations, and Unipolar n-Type Transistor Performance
Development of high-performance unipolar n-type organic semiconductors still remains as a great challenge. In this work, all-acceptor bithiophene imide-based ladder-type small molecules BTIn and semiladder-type homopolymers PBTIn (n = 1–5) w... -
Dendrite-Embedded Platinum–Nickel Multiframes as Highly Active and Durable Electrocatalyst toward the Oxygen Reduction Reaction
Hyukbu Kwon(석사과정) Jongsik Park(박사과정) Pt-based nanoframe catalysts have been explored extensively due to their superior activity toward the oxygen reduction reaction (ORR). Herein, we report the synthesis of Pt–Ni multiframes, which ... -
Mid-Infrared Intraband Transition of Metal Excess Colloidal Ag2Se Nanocrystals
Mihyeon Park(석사과정) Dongsun Choi(박사과정) Steady-state intraband transition, which is a promising electronic transition of a colloidal quantum dot along with the band-gap transition, had been a long-standing challenge. The steady-state ... -
Enhanced Electron Transfer Mediated by Conjugated Polyelectrolyte and Its Application to Washing-Free DNA Detection
Ji-Eun Jeong (박사과정) Direct electron transfer between a redox label and an electrode requires a very short working distance (<1-2 nm), and in general an affinity biosensor based on the direct electron transfer requires a finely smoothed ... -
Vertex-reinforced PtCuCo ternary nanoframes as efficient and stable electrocatalysts for the oxygen reduction reaction and the methanol oxidation reaction
Taehyun Kwon(박사과정) / Minki Jun (박사과정) Noble metal binary alloy nanoframes have emerged as a new class of fuel cell electrocatalysts because of their intrinsic high catalytic surface area and accompanied high catalytic activity. Howe... -
Molecular Role of Ca2+ and Hard Divalent Metal Cations on Accelerated Fibrillation and Interfibrillar Aggregation of α-Synuclein
Jong Yoon Han(박사과정) / Tae Su Choi(Post doc.) α-Synuclein (αSyn) is an intrinsically disordered protein, the aggregation of which is highly related to the pathology of diverse α-synucleinopathies. Various hard divalent metal cations have... -
Supramolecular Modulation of Structural Polymorphism in Pathogenic α-Synuclein Fibrils Using Cu(II) Coordination
Tae Su Choi(Post doc.) / Jong Yoon Han(박사과정) Structural variation of α-synuclein (αSyn) fibrils has been linked to the diverse etiologies of synucleinopathies. However, little is known about what specific mechanism provides αSyn fibrils... -
Recent Progress in the Chemistry of Pyridazinones for Functional Group Transformations
Seohyun Kang(석사과정) While N-hetereocycles have received significant attention in organic synthesis and other research fields, the chemistry of pyridazine, six-membered aromatic ring with adjacent two nitrogen atoms, and its derivatives ... -
Maskless Arbitrary Writing of Molecular Tunnel Junctions
Seo Eun Byeon(석사과정) / Miso Kim(석사과정) Since fabricating geometrically well-defined, noninvasive, and compliant electrical contacts over molecular monolayers is difficult, creating molecular-scale electronic devices that function in h... -
Single Component Organic Solar Cells Based on Oligothiophene-Fullerene Conjugate
Thanh Luan Nguyen(Post doc.) A new donor (D)–acceptor (A) conjugate, benzodithiophene-rhodanine–[6,6]-phenyl-C61 butyric acid methyl ester (BDTRh–PCBM) comprising three covalently linked blocks, one of p-type oligothiophene containing BDTRh... -
Lanthanide metal-assisted synthesis of rhombic dodecahedral MNi (M=Ir and Pt) nanoframes toward efficient oxygen evolution catalysis
Haneul Jin(박사과정) / Yongju Hong(박사과정) Mixed metal alloy nanoframeworks have shown a great promise as electrocatalysts in water electrolyzers and fuel cells. Although a limited number of mixed metal alloy nanoframeworks have been synt... -
Radially Phase Segregated PtCu@PtCuNi Dendrite@Frame Nanocatalyst for the Oxygen Reduction Reaction
Hyukbu Kwon(석사과정) / Jongsik Park(박사과정) Pt-based alloy nanoframes have shown a great potential as electrocatalysts toward oxygen reduction reaction (ORR) in fuel cells. However, the intrinsically infirm nanoframes could be severely d... -
Collision Cross Sections and Ion Structures: Development of a General Calculation Method via High-quality Ion Mobility Measurements and Theoretical Modeling
Ion mobility mass spectrometry (IM-MS) has become an important tool for the structural investigation of ions in the gas phase. Accurate theoretical evaluation of ion collision cross sections (CCSs) is essential for the effective application... -
Total Syntheses of Arcyriaflavin A and Calothrixin B Using 2,2′-Bisindole-3-acetic Acid Derivative as a Common Intermediate
Sungjong Lee(석사과정) / Kyung-Hee Kim(박사과정) A new protocol for the synthesis of 2,2′-bisindole-3-acetic acid derivatives from aldimines derived from 2-aminocinnamic acid derivatives and indole-2-carboxaldehyde was developed via a cyani... -
Synthesis, Characterization, and Efficient Catalytic Activities of a Nickel(II) Porphyrin: Remarkable Solvent and Substrate Effects on Participation of Multiple Active Oxidants
A new nickel(II) porphyrin complex, [NiII(porp)] (1), has been synthesized and characterized by 1H NMR, 13C NMR and mass spectrometry analysis. This NiII porphyrin complex 1 quantitatively catalyzed the epoxidation reaction of a wide range o... -
Molecular Insights into Human Serum Albumin as a Receptor of Amyloid-β in the Extracellular Region
Tae Su Choi(Post doc.) Regulation of amyloid-β (Aβ) aggregation by metal ions and proteins is essential for understanding the pathology of Alzheimer’s disease (AD). Human serum albumin (HSA), a regulator of metal and protein transportation,... -
Two Regioisomeric π-Conjugated Small Molecules: Synthesis, Photophysical, Packing and Optoelectronic Properties
Two Regioisomeric π-Conjugated Small Molecules: Synthesis, Photophysical, Packing and Optoelectronic Properties Dae Hee Lee(박사과정) / Thanh Luan Nguyen(Post doc.) Two regioisomeric D1-A-D-A-D1 type π-conjugated molecules (1,4-bis{5-[4-(5-f... -
Major Electronic Transition Shift from Bandgap to Localized Surface Plasmon Resonance in CdxHg1-xSe Alloy Nanocrystals
Dongsun Choi(박사과정) / Bitna Yonn(석사과정) CdxHg1-xSe alloy nanocrystals are obtained from CdSe semiconductor nanocrystals via cation exchange. By varying the composition during the exchange process, the CdxHg1-xSe alloy nanocrystals off... -
Rational Design of In Vivo Tau Tangle-Selective Near Infrared Fluorophores: Expanding the BODIPY Universe
The elucidation of the cause of Alzheimer’s disease remains one of the greatest questions in neurodegenerative research. The lack of highly reliable low-cost sensors to study the structural changes in key proteins during the progres-sion of ... -
Achieving Highly Efficient Nonfullerene Organic Solar Cells with Improved Intermolecular Interaction and Open-Circuit Voltage
A new acceptor–donor–acceptor-structured nonfullerene acceptor ITCC (3,9-bis(4-(1,1-dicyanomethylene)-3-methylene-2-oxo-cyclopenta[b]thiophen)-5,5,11,11-tetrakis(4-hexylphenyl)-dithieno[2,3-d′:2,3-d′]-s-indaceno[1,2-b:5,6-b′]-dithiophene) is...