Rod-shaped Assemblies Research Articles

Structural plasticity of bacterial ESCRT-III protein PspA in higher-order assemblies.

Eukaryotic members of the endosome sorting complex required for transport-III (ESCRT-III) family have been shown to form diverse higher-order assemblies. The bacterial phage shock protein A (PspA) has been identified as a member of the ESCRT-III superfamily, and PspA homo-oligomerizes to form rod-shaped assemblies. As observed for eukaryotic ESCRT-III, PspA forms tubular assemblies of varying diameters. Using electron cryo-electron microscopy, we determined 61 Synechocystis PspA structures and observed in molecular detail how the structural plasticity of PspA rods is mediated by conformational changes at three hinge regions in the monomer and by the fixed and changing molecular contacts between protomers. Moreover, we reduced and increased the structural plasticity of PspA rods by removing the loop connecting helices α3/α4 and the addition of nucleotides, respectively. Based on our analysis of PspA-mediated membrane remodeling, we suggest that the observed mode of structural plasticity is a prerequisite for the biological function of ESCRT-III members.

Zinc-Induced Luminescent l-Valine-Based Pseudopeptidic Soft Bioinspired Materials for Precise Tuning of Nanoassembly.

Pseudopeptide-based bioinspired materials are emerging for selective recognition of biologically significant analytes and are applicable in the modern nanoscience field. Therefore, we have developed novel multifunctional C2-symmetric soft pseudopeptides by amino acid l-valine and salicylaldehyde fragments using a series of aliphatic linkers. They are highly selective and sensitive to Zn (II) ions under physiological conditions and reveal significant fluorescence enhancement with the PET mechanism. The molecular self-assembly shows zinc-induced morphological transformation of the rod-shaped assembly into a chain-like morphology. Such a metal-induced hierarchical nano-assembly may have relevance for specific nanobiotechnology applications.

Molecular Assembled Electrocatalyst for Highly Selective CO2 Fixation to C2+ Products.

In certain metalloenzymes, multimetal centers with appropriate primary/secondary coordination environments allow carbon-carbon coupling reactions to occur efficiently and with high selectivity. This same function is seldom realized in molecular electrocatalysts. Herein we synthesized rod-shaped nanocatalysts with multiple copper centers through the molecular assembly of a triphenylphosphine copper complex (CuPPh). The assembled molecular CuPPh catalyst demonstrated excellent electrochemical CO2 fixation performance in aqueous solution, yielding high-value C2+ hydrocarbons (ethene) and oxygenates (ethanol) as the main products. Using density functional theory (DFT) calculations, in situ X-ray absorption spectroscopy (XAS) and quasi-in situ X-ray photoelectron spectroscopy (XPS), and reaction intermediate capture, we established that the excellent catalytic performance originated from the large number of double copper centers in the rod-shaped assemblies. Cu-Cu distances in the absence of CO2 were as long as 7.9 Å, decreasing substantially after binding CO2 molecules indicating dynamic and cooperative function. The double copper centers were shown to promote carbon-carbon coupling via a CO2 transfer-coupling mechanism involving an oxalate (OOC-COO) intermediate, allowing the efficient production of C2+ products. The assembled CuPPh nanorods showed high activity, excellent stability, and a high Faradaic efficiency (FE) to C2+ products (65.4%), with performance comparable to state-of-the-art copper oxide-based catalysts. To our knowledge, our findings demonstrate that harnessing metalloenzyme-like properties in molecularly assembled catalysts can greatly improve the selectivity of CO2RR, promoting the rational design of improved CO2 reduction catalysts.

TNF receptor agonists induce distinct receptor clusters to mediate differential agonistic activity

Monoclonal antibodies (mAb) and natural ligands targeting costimulatory tumor necrosis factor receptors (TNFR) exhibit a wide range of agonistic activities and antitumor responses. The mechanisms underlying these differential agonistic activities remain poorly understood. Here, we employ a panel of experimental and clinically-relevant molecules targeting human CD40, 4-1BB and OX40 to examine this issue. Confocal and STORM microscopy reveal that strongly agonistic reagents induce clusters characterized by small area and high receptor density. Using antibody pairs differing only in isotype we show that hIgG2 confers significantly more receptor clustering than hIgG1 across all three receptors, explaining its greater agonistic activity, with receptor clustering shielding the receptor-agonist complex from further molecular access. Nevertheless, discrete receptor clustering patterns are observed with different hIgG2 mAb, with a unique rod-shaped assembly observed with the most agonistic mAb. These findings dispel the notion that larger receptor clusters elicit greater agonism, and instead point to receptor density and subsequent super-structure as key determinants.

Solution inheritance of CoC 2 O 4 ·2H 2 O rods to nanoparticle-assembled Co 3 O 4 rods

Abstract An inheritance strategy for fabricating nanoparticle-assembled Co 3 O 4 rods was reported with CoC 2 O 4 ·2H 2 O rods as self-template in aqueous solution. The substitution–oxidation process (CoC 2 O 4 ·2H 2 O → Co(OH) 2 → Co 3 O 4 ) was investigated by X-ray diffraction (XRD), scanning electron microscopy (SEM) and Fourier transform infrared spectroscopy (FT–IR). The amount of NaOH, crystal characters of Co(OH) 2 intermediates and growth time of Co 3 O 4 play important roles on the formation of the nanoparticle-assembled Co 3 O 4 rods. Trace residual CoC 2 O 4 ·2H 2 O is necessary for keeping Co 3 O 4 nanoparticles in rod-shaped assembly. Comparing with the Co 3 O 4 rods obtained by calcining CoC 2 O 4 ·2H 2 O rods at high temperature, the solution synthesized nanoparticle-assembled Co 3 O 4 rods performed higher activities on photocatalytic degradation of rhodamine B (RhB) and catalytic decomposition of ammonium perchlorate (AP).

Rod-shaped nanostructures based on superparamagnetic nanocrystals as viscosity sensors in liquid

Superparamagnetic nanostructures are becoming increasingly important as tools for biological and medical applications. We report the study of the movement of rod-shaped assemblies of superparamagnetic nanocrystals under the action of a rotating magnetic field. The dynamic was characterized by means of light scattering detection at different frequencies and for different values of the intensity of the applied external field. The possibility to correlate the motion to the viscosity of the medium is used to monitor viscosity changes inside the liquid. We propose this technique as a valuable tool to monitor viscosity at microscale for application in biological studies.

The Structure of Neurexin 1α Reveals Features Promoting a Role as Synaptic Organizer

α-neurexins are essential synaptic adhesion molecules implicated in autism spectrum disorder and schizophrenia. The α-neurexin extracellular domain consists of six LNS domains interspersed by three EGF-like repeats and interacts with many different proteins in the synaptic cleft. To understand how α-neurexins might function as synaptic organizers, we solved the structure of the neurexin 1α extracellular domain (n1α) to 2.65 Å. The L-shaped molecule can be divided into a flexible repeat I (LNS1-EGF-A-LNS2), a rigid horseshoe-shaped repeat II (LNS3-EGF-B-LNS4) with structural similarity to so-called reelin repeats, and an extended repeat III (LNS5-EGF-B-LNS6) with controlled flexibility. A 2.95 Å structure of n1α carrying splice insert SS#3 in LNS4 reveals that SS#3 protrudes as a loop and does not alter the rigid arrangement of repeat II. The global architecture imposed by conserved structural features enables α-neurexins to recruit and organize proteins in distinct and variable ways, influenced by splicing, thereby promoting synaptic function.

Nonamphiphilic Assembly in Water: Polymorphic Nature, Thread Structure, and Thermodynamic Incompatibility

Self-assembly of large quantities of entirely water-soluble molecules is entropically challenging. In this work, we describe the design and synthesis of water-soluble aromatic (dichromonyl) molecules that can form nonamphiphilic assemblies and the so-called chromonic liquid crystal phase in water. We discover a new molecule, 5'DSCG-diviol, that exhibits a large birefringent phase, and we show that the formation of this unique class of nonamphiphilic lyotropic liquid crystal shares enormous similarity to the polymorphism observed for crystal formation. Small-angle neutron scattering (SANS) revealed a concentration-independent rod-shaped assembly at concentrations below and above the formation of liquid crystal phase. Adding a small percentage of monoanionic aromatic molecules to the liquid crystal resulted in the elimination of the liquid crystal phase, but addition of dianionic aromatic molecules retained the liquid crystal phase. Together, these results suggest a new assembly structure for nonamphiphilic molecules in water, which is comprised of long threads of small molecules connected by salt bridges stacked over aromatic groups, with the molecular threads heavily hydrated with solvent water. Furthermore, mixing molecules with different structures can result in new liquid crystalline materials, or in segregation of the molecules into different solvation volumes, each of which contains only one type of molecule. The unusual thermodynamic incompatibility of entirely water-soluble molecules also supports the model of molecular threads, in which two polymer-like assemblies do not mix.

The unfolded protein response signals through high-order assembly of Ire1

Aberrant folding of proteins in the endoplasmic reticulum activates the bifunctional transmembrane kinase/endoribonuclease Ire1. Ire1 excises an intron from HAC1 messenger RNA in yeasts and Xbp1 messenger RNA in metozoans encoding homologous transcription factors. This non-conventional mRNA splicing event initiates the unfolded protein response, a transcriptional program that relieves the endoplasmic reticulum stress. Here we show that oligomerization is central to Ire1 function and is an intrinsic attribute of its cytosolic domains. We obtained the 3.2-A crystal structure of the oligomer of the Ire1 cytosolic domains in complex with a kinase inhibitor that acts as a potent activator of the Ire1 RNase. The structure reveals a rod-shaped assembly that has no known precedence among kinases. This assembly positions the kinase domain for trans-autophosphorylation, orders the RNase domain, and creates an interaction surface for binding of the mRNA substrate. Activation of Ire1 through oligomerization expands the mechanistic repertoire of kinase-based signalling receptors.

Structural and Photophysical Properties of Self-Assembled Porphyrin Nanoassemblies Organized by Ethylene Glycol Derivatives

We demonstrate an ability to control the structures and photodynamics of porphyrin-based nanoassemblies via solvent mixture technique. Surfactants such as ethylene glycol (EG) derivatives with different chain lengths are employed to control the sizes and shapes of nanoparticles composed of meso-substituted tetracarboxyphenyl porphyrin [H2P(CO2H)4] in mixed H2O/THF solvent. With increasing the chain lengths, the diameters of H2P(CO2H)4/EG composite nanoparticles systematically increase in the range of 90−350 nm. In contrast with H2P(CO2H)4/EG composite nanoparticles, pristine H2P(CO2H)4 assemblies show long rod-shaped assemblies with micrometer scales. The porphyrin nanoparticles are stable in solution without precipitation for several days. The nanoparticles exhibit the following optical properties: a large bathochromic shift in the absorption spectra and an increase of the fluorescence quenching properties relative to those for the monomer porphyrin solution. The hierarchical clustering of H2P(CO2H)4 molecules within nanoparticles is caused by the hydrogen bonding and π-stacking effects. The efficient fluorescence quenching of H2P(CO2H)4 is mainly due to the effect of singlet−singlet annihilation of H2P(CO2H)4 moieties within nanoassemblies. We further report the quenching processes of the excited triplet states of H2P(CO2H)4 nanoassemblies. Efficient quenching properties of the excited triplet states of H2P(CO2H)4 moieties are observed in the range of lifetime 26−100 ns, which is largely dependent on the sizes of nanoparticles. These quenching processes can be also analyzed by triplet−triplet annihilation theory.

Chronophin Mediates an ATP-Sensing Mechanism for Cofilin Dephosphorylation and Neuronal Cofilin-Actin Rod Formation

Actin and its key regulatory component, cofilin, are found together in large rod-shaped assemblies in neurons subjected to energy stress. Such inclusions are also enriched in Alzheimer's disease brain, and appear in transgenic models of neurodegeneration. Neuronal insults, such as energy loss and/or oxidative stress, result in rapid dephosphorylation of the cellular cofilin pool prior to its assembly into rod-shaped inclusions. Although these events implicate a role for phosphatases in cofilin rod formation, a mechanism linking energy stress, phosphocofilin turnover, and subsequent rod assembly has been elusive. We demonstrate the ATP-sensitive interaction of the cofilin phosphatase chronophin (CIN) with the chaperone hsp90 to form a biosensor that mediates cofilin/actin rod formation. Our results suggest a model whereby attenuated interactions between CIN and hsp90 during ATP depletion enhance CIN-dependent cofilin dephosphorylation and consequent rod assembly, thereby providing a mechanism for the formation of pathological actin/cofilin aggregates during neurodegenerative energy flux.

Rod‐Shaped Assemblies of FePt‐PtTe2 through Dynamic Templating

Rod-shaped assemblies of FePt nanoparticles embedded amidst PtTe2 nanoplatelets, formed by co-precipitation in the presence of sucrose and trioctylphosphine oxide. The (001) planes in each of the PtTe2 nanoplatelets are stacked along directions close to the nanorod axis. Separate precipitation of FePt or PtTe2 under identical conditions yield spheres or randomly shaped clusters platelets, underscoring the key influence of co-precipitation on the morphology of the nanostructure assembly.

Structure of a Central Component of the Yeast Kinetochore: The Spc24p/Spc25p Globular Domain

The Ndc80 complex, a kinetochore component conserved from yeast to humans, is essential for proper chromosome alignment and segregation during mitosis. It is an approximately 570 A long, rod-shaped assembly of four proteins--Ndc80p (Hec1), Nuf2p, Spc24p, and Spc25p--with globular regions at either end of a central shaft. The complex bridges from the centromere-proximal inner kinetochore layer at its Spc24/Spc25 globular end to the microtubule binding outer kinetochore layer at its Ndc80/Nuf2 globular end. We report the atomic structures of the Spc24/Spc25 globular domain, determined both by X-ray crystallography at 1.9 A resolution and by NMR. Spc24 and Spc25 fold tightly together into a single globular entity with pseudo-2-fold symmetry. Conserved residues line a common hydrophobic core and the bottom of a cleft, indicating that the functional orthologs from other eukaryotes will have the same structure and suggesting a docking site for components of the inner kinetochore.

Parallel assembly of dipolar columns composed of a stacked cyclic tri-β-peptide

A novel cyclic trimer of a beta-amino acid, trans-2-aminocyclohexylcarboxylic acid, was synthesized and its conformation and ability to form assemblies investigated. FT-IR and NMR measurements and computational calculations showed that this cyclic tri-beta-peptide has a C3-symmetric conformation with trans amide groups. A notable feature of the conformation is a vertical and parallel orientation of the three amide groups to the cyclic skeleton. The cyclic tri-beta-peptide was crystallized from a solution in trifluoroacetic acid-methanol (or trifluoroacetic acid-water) to yield a rod-shaped molecular assembly, as observed by TEM. The electron crystallography of the rod-shaped assembly both in suspension and in ultrathin cross-section revealed that the cyclic tri-beta-peptides were stacked up to form molecular columns, and that a two-fold screw symmetry operation along the column direction was present in the unit cell, which contained two cyclic tri-beta-peptides. This indicates that all the amide groups are oriented in the same direction. Since any two molecular columns are staggered by a quarter of a c-axis length and aligned parallel to each other, the dipole moments of the columns are aligned to enhance the strength additively in the whole assembly.