The outcome of synthetic procedures for crystalline organic materials strongly depends on the first steps along the molecular self‐assembly pathway, a process we know as crystal nucleation. New ...experimental techniques and computational methodologies have spurred significant interest in understanding the detailed molecular mechanisms by which nuclei form and develop into macroscopic crystals. Although classical nucleation theory (CNT) has served well in describing the kinetics of the processes involved, new proposed nucleation mechanisms are additionally concerned with the evolution of structure and the competing nature of crystallization in polymorphic systems. In this Review, we explore the extent to which CNT and nucleation rate measurements can yield molecular‐scale information on this process and summarize current knowledge relating to molecular self‐assembly in nucleating systems.
Everything starts out small: The synthesis of organic materials depends strongly on the first steps of molecular self‐assembly during crystal nucleation. This Review summarizes current knowledge on these processes. Self‐association in different solvents can lead to the creation of different building blocks, which form differently packed nuclei and thus in each case specific crystalline phases.
Collagen fibrils represent a unique case of protein folding and self‐association. We have recently successfully developed triple‐helical peptides that can further self‐assemble into collagen‐mimetic ...mini‐fibrils. The 35 nm axially repeating structure of the mini‐fibrils, which is designated the d‐period, is highly reminiscent of the well‐known 67 nm D‐period of native collagens when examined using TEM and atomic force spectroscopy. We postulate that it is the pseudo‐identical repeating sequence units in the primary structure of the designed peptides that give rise to the d‐period of the quaternary structure of the mini‐fibrils. In this work, we characterize the self‐assembly of two additional designed peptides: peptide Col877 and peptide Col108rr. The triple‐helix domain of Col877 consists of three pseudo‐identical amino acid sequence units arranged in tandem, whereas that of Col108rr consists of three sequence units identical in amino acid composition but different in sequence. Both peptides form stable collagen triple helices, but only triple helices Col877 self‐associate laterally under fibril forming conditions to form mini‐fibrils having the predicted d‐period. The Co108rr triple helices, however, only form nonspecific aggregates having no identifiable structural features. These results further accentuate the critical involvement of the repeating sequence units in the self‐assembly of collagen mini‐fibrils; the actual amino acid sequence of each unit has only secondary effects. Collagen is essential for tissue development and function. This novel approach to creating collagen‐mimetic fibrils can potentially impact fundamental research and have a wide range of biomedical and industrial applications.
Membrane‐less organelles in cells are large, dynamic protein/protein or protein/RNA assemblies that have been reported in some cases to have liquid droplet properties. However, the molecular ...interactions underlying the recruitment of components are not well understood. Herein, we study how the ability to form higher‐order assemblies influences the recruitment of the speckle‐type POZ protein (SPOP) to nuclear speckles. SPOP, a cullin‐3‐RING ubiquitin ligase (CRL3) substrate adaptor, self‐associates into higher‐order oligomers; that is, the number of monomers in an oligomer is broadly distributed and can be large. While wild‐type SPOP localizes to liquid nuclear speckles, self‐association‐deficient SPOP mutants have a diffuse distribution in the nucleus. SPOP oligomerizes through its BTB and BACK domains. We show that BTB‐mediated SPOP dimers form linear oligomers via BACK domain dimerization, and we determine the concentration‐dependent populations of the resulting oligomeric species. Higher‐order oligomerization of SPOP stimulates CRL3SPOP ubiquitination efficiency for its physiological substrate Gli3, suggesting that nuclear speckles are hotspots of ubiquitination. Dynamic, higher‐order protein self‐association may be a general mechanism to concentrate functional components in membrane‐less cellular bodies.
Synopsis
SPOP, a ubiquitin ligase substrate receptor and tumor suppressor, self‐associates indefinitely into large oligomers via the synergistic function of its tandem dimerization domains. The resulting oligomers are recruited to liquid nuclear speckles, likely generating hotspots of SPOP‐mediated ubiquitination.
SPOP localizes to liquid nuclear bodies.
Self‐association‐deficient SPOP mutants lose their localization to nuclear speckles.
SPOP forms labile higher‐order oligomers through tandem self‐association domains and an isodesmic mechanism.
The BTB self‐association‐deficient mutant has a dominant‐negative effect on Hedgehog signaling in the developing fly wing.
Dynamic, higher‐order self‐association may be a general mechanism to concentrate functional components in membrane‐less cellular bodies.
Self‐association of the ubiquitin ligase adaptor and tumor suppressor SPOP is required for its recruitment to liquid nuclear bodies, likely generating hotspots of SPOP‐mediated ubiquitination.
The aim of this review is to present precisely defined amphiphilic dendrons (dendritic wedges), generally based on known dendrimers (aryl ether, amidoamine, amide, quaternary carbon, alkyl ether, ...ester, main group element), their self‐association properties, and their uses, in particular for encapsulation and delivery of bioactive entities. In most cases, the hydrophilic part is constituted by the terminal functions of the dendrons, whereas one or two hydrophobic tails are linked to the core. Read more in the Review article by E. Apartsin and A.‐M. Caminade on page 17976 ff.
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Experimental information on the molecular scale structure of ionic liquid interfaces is controversial, giving rise to two competing scenarios, namely the double layer-like and ...“chessboard”-like structures. This issue can be resolved by computer simulation methods, at least for the underlying molecular model. Systematically changing the anion type can elucidate the relative roles of electrostatic interactions, hydrophobic (or, strictly speaking, apolar) effects and steric restrictions on the interfacial properties.
Molecular dynamics simulation is combined with intrinsic analysis methods both at the molecular and atomic levels, supplemented by Voronoi analysis of self-association.
We see no evidence for the existence of a double-layer-type arrangement of the ions, or for their self-association at the surface of the liquid. Instead, our results show that cation chains associate into apolar domains that protrude into the vapour phase, while charged groups form domains that are embedded in this apolar environment at the surface. However, the apolar chains largely obscure the cation groups, to which they are bound, while the smaller and more mobile anions can more easily access the free surface, leading to a somewhat counterintuitive net excess of negative charge at the interface. Importantly, this excess charge could only be identified by applying intrinsic analysis.
Traditional rechargeable Zn batteries fail to work in cold regions due to the high freezing point (Tf) and severe corrosivity of the aqueous electrolytes with excessive association (solvent‐solvent ...and solute‐solvent interactions). In this study, a nonflammable weak‐associated electrolyte (WASE) consisting of ZnCl2 salt and methanol/dichloromethane mixture as a solvent is developed to achieve high reversible Zn plating/stripping at low temperatures. The low self‐association interaction of the mixed solvent not only endures WASE with a low Tf of −119.2 °C but also facilitates the desolvation of interfacial Zn2+ and induces smooth Zn plating at low temperatures. Moreover, the water‐free WASE inhibits the hydrolysis of ZnCl2 and thus restrains the corrosion of Zn electrodes. Thanks to the above merits, the Zn||Zn, Zn||Cu, and Zn||polyaniline cells with WASE exhibit superb electrochemical performance at temperatures as low as −78.5 °C.
A nonflammable weak‐association‐state electrolyte (WASE) is designed for rechargeable Zn batteries (RZBs). Thanks to the suppressed self‐association and the moderate solvation capability toward Zn2+, the as‐designed WASE exhibits an ultralow freezing point of −119.2 °C and enhanced Zn compatibility compared with 2 m ZnCl2 in water, enabling high‐stability RZBs at −78.5 °C.
The mechanistic modeling of preparative liquid chromatography is still a challenging task. Nonideal thermodynamic conditions may require activity coefficients for the mechanistic description of ...preparative chromatography. In this work, a chromatographic cation exchange step with a polypeptide having a complex elution behavior in low and high loading situations is modeled. Model calibration in the linear range of the isotherm is done by applying counterion‐induced linear gradient elution experiments between pH 3.3 and 4.3. Inverse fitting with column loads up to 25 mg/mLCV is performed for parameter estimation in the nonlinear range. The polypeptide elution peak shows an anti‐Langmuirian behavior with fronting under low loading conditions and a switch to a Langmuirian behavior with increasing load. This unusual elution behavior could be described with an extended version of the sigmoidal Self‐Association isotherm including two activity coefficients for the polypeptide and counterion in solution. The activity coefficient of the solute polypeptide shows a strong influence on the model parameters and is crucial in the linear and nonlinear range of the isotherm. The modeling procedure results in a unique and robust model parameter set that is sufficient to describe the complex elution behavior and allows modeling over the full isotherm range.
Eukaryotic cells have a continuous transit of macromolecules between the cytoplasm and the nucleus. Several carrier proteins are involved in this transport. One of them is importin α, which must form ...a complex with importin β to accomplish its function, by domain-swapping its 60-residue-long N terminus. There are several human isoforms of importin α; among them, importin α3 has a particularly high flexibility.
We studied the conformational stability of intact importin α3 (Impα3) and its truncated form, where the 64-residue-long, N-terminal importin-β-binding domain (IBB) has been removed (ΔImpα3), in a wide pH range, with several spectroscopic, biophysical, biochemical methods and with molecular dynamics (MD).
Both species acquired native-like structure between pH 7 and 10.0, where Impα3 was a dimer (with an apparent self-association constant of ~10 μM) and ΔImpα3 had a higher tendency to self-associate than the intact species. The acquisition of secondary, tertiary and quaternary structure, and the burial of hydrophobic patches, occurred concomitantly. Both proteins unfolded irreversibly at physiological pH, by using either temperature or chemical denaturants, through several partially folded intermediates. The MD simulations support the presence of these intermediates.
The thermal stability of Impα3 at physiological pH was very low, but was higher than that of ΔImpα3. Both proteins were stable in a narrow pH range, and they unfolded at physiological pH populating several intermediate species.
The low conformational stability explains the flexibility of Impα3, which is needed to carry out its recognition of complex cargo sequences.
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•Human importin α3 had low stability and self-associated in solution.•Its truncated species, without the importin β-binding region, had a lower conformational stability.•Both species unfolded through the present of several intermediates with non-native structure.•Both species were stable in a narrow pH range (between pH 7 and 10).
Verticillium wilt is one of the most devasting diseases for many plants, leading to global economic loss. Cotton is known to be vulnerable to its fungal pathogen, Verticillium dahliae, yet the ...related genetic mechanism remains unknown.
By genome-wide association studies of 419 accessions of the upland cotton, Gossypium hirsutum, we identify ten loci that are associated with resistance against Verticillium wilt. Among these loci, SHZDI1/SHZDP2/AYDP1 from chromosome A10 is located on a fragment introgressed from Gossypium arboreum. We characterize a large cluster of Toll/interleukin 1 (TIR) nucleotide-binding leucine-rich repeat receptors in this fragment. We then identify a dual-TIR domain gene from this cluster, GhRVD1, which triggers an effector-independent cell death and is induced by Verticillium dahliae. We confirm that GhRVD1 is one of the causal gene for SHZDI1. Allelic variation in the TIR domain attenuates GhRVD1-mediated resistance against Verticillium dahliae. Homodimerization between TIR1-TIR2 mediates rapid immune response, while disruption of its αD- and αE-helices interface eliminates the autoactivity and self-association of TIR1-TIR2. We further demonstrate that GhTIRP1 inhibits the autoactivity and self-association of TIR1-TIR2 by competing for binding to them, thereby preventing the resistance to Verticillium dahliae.
We propose the first working model for TIRP1 involved self-association and autoactivity of dual-TIR domain proteins that confer compromised pathogen resistance of dual-TIR domain proteins in plants. The findings reveal a novel mechanism on Verticillium dahliae resistance and provide genetic basis for breeding in future.
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