F-type ATP synthases play a key role in oxidative and photophosphorylation processes generating adenosine triphosphate (ATP) for most biochemical reactions in living organisms. In contrast to the ...mitochondrial Fsub.OFsub.1-ATP synthases, those of chloroplasts are known to be mostly monomers with approx. 15% fraction of oligomers interacting presumably non-specifically in a thylakoid membrane. To shed light on the nature of this difference we studied interactions of the chloroplast ATP synthases using small-angle X-ray scattering (SAXS) method. Here, we report evidence of I-shaped dimerization of solubilized Fsub.OFsub.1-ATP synthases from spinach chloroplasts at different ionic strengths. The structural data were obtained by SAXS and demonstrated dimerization in response to ionic strength. The best model describing SAXS data was two ATP-synthases connected through Fsub.1/Fsub.1′ parts, presumably via their δ-subunits, forming “I” shape dimers. Such I-shaped dimers might possibly connect the neighboring lamellae in thylakoid stacks assuming that the Fsub.OFsub.1 monomers comprising such dimers are embedded in parallel opposing stacked thylakoid membrane areas. If this type of dimerization exists in nature, it might be one of the pathways of inhibition of chloroplast Fsub.OFsub.1-ATP synthase for preventing ATP hydrolysis in the dark, when ionic strength in plant chloroplasts is rising. Together with a redox switch inserted into a γ-subunit of chloroplast Fsub.OFsub.1 and lateral oligomerization, an I-shaped dimerization might comprise a subtle regulatory process of ATP synthesis and stabilize the structure of thylakoid stacks in chloroplasts.
Keywords: aluminum; DFT calculations; Keggin clusters; polycations; self-condensation Keggin-type polyaluminum cations belong to a unique class of compounds with their large positive charge, hydroxo ...bridges, and divergent isomerization/oligomerization. Previous reports indicated that oligomerization of this species can only occur through one isomer (δ), but herein we report the isolation of largest Keggin-type cluster that occurs through self-condensation of four ?-isomers ?-GeAl.sub.12.sup.8+ to form Ge.sub.4O.sub.16Al.sub.48(OH).sub.108(H.sub.2O).sub.24.sup.20+ cluster (Ge.sub.4Al.sub.48). The cluster was crystallized and structurally characterized by single-crystal X-ray diffraction (SCXRD) and the elemental composition was confirmed by ICP-MS and SEM-EDS. Additional dynamic light scattering experiments confirms the presence of the Ge.sub.4Al.sub.48 in thermally aged solutions. DFT calculations reveal that a single atom Ge substitution in tetrahedral site of ?-isomer is the key for the formation of Ge.sub.4Al.sub.48 because it activates deprotonation at key surface sites that control the self-condensation process. Article Note: A previous version of this manuscript has been deposited on a preprint server ( Supporting information: Additional Supporting Information may be found in the online version of this article As a service to our authors and readers, this journal provides supporting information supplied by the authors. Such materials are peer reviewed and may be re-organized for online delivery, but are not copy-edited or typeset. Technical support issues arising from supporting information (other than missing files) should be addressed to the authors. CAPTION(S): Supplementary Byline: Mohammad Shohel, Jennifer L. Bjorklund, Jack A. Smith, Dmytro V. Kravchuk, Sara E. Mason, Tori Z. Forbes
The crystal structure of (1,2,3-trimethylpyridnium)sub.2Cusub.5Brsub.12 provides the second reported example of a fully halogenated, linear, quasi-planar, bibridged pentacopper(II) oligomer. The ...oligomers are aggregated into crosshatched layers that defy traditional notions and notations for quasi-planar oligomer stacking. The regularly arranged voids in the layers are occupied by inversion-related organic cation pairs similar to eggs in an egg-tray. The cross-hatched layer structure arises from a particular stacking of mixed organic cation/pentacopper oligomer sheets. The sheets consist of oligomers placed in a herringbone arrangement separated by zipper-like ribbons of organic cations in a structural motif similar to that found in other 1,2,3- or 1,2,6-trimethylpyridinium halidocuprate(II) structures. Alternative stacking of the sheets leads, on the other hand, to a conventional stacking pattern that conforms to traditional stacking descriptions. Interpretation of these structures in terms of the stacking of mixed cation/anion sheets, as is often performed for ABXsub.3 systems, provides a complementary method for understanding these structures as well as providing a means to describe systems that are not easily described by traditional stacking notation.
Keywords: aluminum; DFT calculations; Keggin clusters; polycations; self-condensation Keggin-type polyaluminum cations belong to a unique class of compounds with their large positive charge, hydroxo ...bridges, and divergent isomerization/oligomerization. Previous reports indicated that oligomerization of this species can only occur through one isomer (δ), but herein we report the isolation of largest Keggin-type cluster that occurs through self-condensation of four ?-isomers ?-GeAl.sub.12.sup.8+ to form Ge.sub.4O.sub.16Al.sub.48(OH).sub.108(H.sub.2O).sub.24.sup.20+ cluster (Ge.sub.4Al.sub.48). The cluster was crystallized and structurally characterized by single-crystal X-ray diffraction (SCXRD) and the elemental composition was confirmed by ICP-MS and SEM-EDS. Additional dynamic light scattering experiments confirms the presence of the Ge.sub.4Al.sub.48 in thermally aged solutions. DFT calculations reveal that a single atom Ge substitution in tetrahedral site of ?-isomer is the key for the formation of Ge.sub.4Al.sub.48 because it activates deprotonation at key surface sites that control the self-condensation process. Article Note: A previous version of this manuscript has been deposited on a preprint server ( Supporting information: Additional Supporting Information may be found in the online version of this article As a service to our authors and readers, this journal provides supporting information supplied by the authors. Such materials are peer reviewed and may be re-organized for online delivery, but are not copy-edited or typeset. Technical support issues arising from supporting information (other than missing files) should be addressed to the authors. CAPTION(S): Supplementary Byline: Mohammad Shohel, Jennifer L. Bjorklund, Jack A. Smith, Dmytro V. Kravchuk, Sara E. Mason, Tori Z. Forbes
Abnormal oligomerization and aggregation of alpha-synuclein (alpha-syn/WT-syn) has been shown to be a precipitating factor in the pathophysiology of Parkinson's disease (PD). Earlier observations on ...the induced-alternative splicing of alpha-syn by Parkinsonism mimetics as well as identification of region specific abnormalities in the transcript levels of 112-synclein (112-syn) in diseased subjects underscores the role of 112-syn in the pathophysiology of PD. In the present study, we sought to identify the aggregation potential of 112-syn in the presence or absence of WT-syn to predict its plausible role in protein aggregation events. Results demonstrate that unlike WT-syn, lack of 28 aa in the C-terminus results in the loss of chaperone-like activity with a concomitant gain in vulnerability to heat-induced aggregation and time-dependent fibrillation. The effects were dose and time-dependent and a significant aggregation of 112-syn was evident at as low as 45#176;C following 10 min of incubation. The heat-induced aggregates were found to be ill-defined structures and weakly positive towards Thioflavin-T (ThT) staining as compared to clearly distinguishable ThT positive extended fibrils resulting upon 24 h of incubation at 37#176;C. Further, the chaperone-like activity of WT-syn significantly attenuated heat-induced aggregation of 112-syn in a dose and time-dependent manner. On contrary, WT-syn synergistically enhanced fibrillation of 112-syn. Overall, the present findings highlight a plausible cross-talk between isoforms of alpha-syn and the relative abundance of these isoforms may dictate the nature and fate of protein aggregates.
Alzheimer’s disease (AD) is the most common form of dementia worldwide, and it contributes up to 70% of cases. AD pathology involves abnormal amyloid beta (Aβ) accumulation, and the link between the ...Aβsub.1-42 structure and toxicity is of major interest. NMDA receptors (NMDAR) are thought to be essential in Aβ-affected neurons, but the role of this receptor in glial impairment is still unclear. In addition, there is insufficient knowledge about the role of Aβ species regarding mitochondrial redox states in neurons and glial cells, which may be critical in developing Aβ-caused neurotoxicity. In this study, we investigated whether different Aβsub.1-42 species—small oligomers, large oligomers, insoluble fibrils, and monomers—were capable of producing neurotoxic effects via microglial NMDAR activation and changes in mitochondrial redox states in primary rat brain cell cultures. Small Aβsub.1-42 oligomers induced a concentration- and time-dependent increase in intracellular Casup.2+ and necrotic microglial death. These changes were partially prevented by the NMDAR inhibitors MK801, memantine, and D-2-amino-5-phosphopentanoic acid (DAP5). Neither microglial intracellular Casup.2+ nor viability was significantly affected by larger Aβsub.1-42 species or monomers. In addition, the small Aβsub.1-42 oligomers caused mitochondrial reactive oxygen species (mtROS)-mediated mitochondrial depolarization, glutamate release, and neuronal cell death. In microglia, the Aβsub.1-42-induced mtROS overproduction was mediated by intracellular calcium ions and Aβ-binding alcohol dehydrogenase (ABAD). The data suggest that the pharmacological targeting of microglial NMDAR and mtROS may be a promising strategy for AD therapy.
Although deep learning has revolutionized protein structure prediction, almost all experimentally characterized de novo protein designs have been generated using physically based approaches such as ...Rosetta. Here, we describe a deep learning-based protein sequence design method, ProteinMPNN, that has outstanding performance in both in silico and experimental tests. On native protein backbones, ProteinMPNN has a sequence recovery of 52.4% compared with 32.9% for Rosetta. The amino acid sequence at different positions can be coupled between single or multiple chains, enabling application to a wide range of current protein design challenges. We demonstrate the broad utility and high accuracy of ProteinMPNN using x-ray crystallography, cryo-electron microscopy, and functional studies by rescuing previously failed designs, which were made using Rosetta or AlphaFold, of protein monomers, cyclic homo-oligomers, tetrahedral nanoparticles, and target-binding proteins.
Well‐defined, fused‐ring aromatic oligomers represent promising candidates for the fundamental understanding and application of advanced carbon‐rich materials, though bottom‐up synthesis and ...structure–property correlation of these compounds remain challenging. In this work, an efficient synthetic route was employed to construct extended benzoktetraphene‐derived oligomers with up to 13 fused rings. The molecular and electronic structures of these compounds were clearly elucidated. Precise correlation of molecular sizes and crystallization dynamics was established, thus demonstrating the pivotal balance between intermolecular interaction and molecular mobility for optimized processing of highly ordered solids of these extended conjugated molecules.
Various methods, such as XRF, XRD, SEM, N.sub.2 adsorption/desorption, NH.sub.3-TPD, and IR spectroscopy of adsorbed pyridine, were used to characterize SAPO-11 samples crystallized from ...Al-isopropoxide as an aluminum source and from SiO.sub.2 with various dispersions (4, 22, and 200 nm) as a silicon source. Decreasing the size of SiO.sub.2 particles was shown to enhance the total concentration of acid sites and to affect the morphology and increase the dispersion of the primary crystals. These SAPO-11 samples were then tested in the oligomerization of alpha-methylstyrene into its valuable dimers. The SAPO sample synthesized using a SiO.sub.2 sol with an average particle size of 4 nm exhibited a higher concentration of strong acid sites and higher accessibility of those sites than the other tested samples. These advantages allowed this SAPO sample to achieve the highest monomer conversion and the highest alpha-methylstyrene dimer selectivity.
Alzheimer's disease (AD) is a progressive disorder in which the most noticeable symptoms are cognitive impairment and memory loss. However, the precise mechanism by which those symptoms develop ...remains unknown. Of note, neuronal loss occurs at sites where synaptic dysfunction is observed earlier, suggesting that altered synaptic connections precede neuronal loss. The abnormal accumulation of amyloid-β (Aβ) and tau protein is the main histopathological feature of the disease. Several lines of evidence suggest that the small oligomeric forms of Aβ and tau may act synergistically to promote synaptic dysfunction in AD. Remarkably, tau pathology correlates better with the progression of the disease than Aβ. Recently, a growing number of studies have begun to suggest that missorting of tau protein from the axon to the dendrites is required to mediate the detrimental effects of Aβ. In this review we discuss the novel findings regarding the potential mechanisms by which tau oligomers contribute to synaptic dysfunction in AD.
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