The walleye (Sander vitreus) is a golden yellow fish that inhabits the Northern American lakes. The recent sightings of the blue walleye and the correlation of its sighting to possible increased UV radiation have been proposed earlier. The underlying molecular basis of its adaptation to increased UV radiation is the presence of a protein (Sandercyanin)-ligand complex in the mucus of walleyes. Degradation of heme by UV radiation results in the formation of Biliverdin IXα (BLA), the chromophore bound to Sandercyanin. We show that Sandercyanin is a monomeric protein that forms stable homotetramers on addition of BLA to the protein. A structure of the Sandercyanin-BLA complex, purified from the fish mucus, reveals a glycosylated protein with a lipocalin fold. This protein-ligand complex absorbs light in the UV region (λ max of 375 nm) and upon excitation at this wavelength emits in the red region (λ max of 675 nm). Unlike all other known biliverdin-bound fluorescent proteins, the chromophore is noncovalently bound to the protein. We provide here a molecular rationale for the observed spectral properties of Sandercyanin.Sandercyanin | walleye | blue protein | red fluorescent protein | UV radiation

The formation of amyloid fibrils and oligomers is a hallmark of several neurodegenerative disorders, including Alzheimer’s disease (AD), and contributes to the disease pathway. To progress our understanding of these diseases at a molecular level, it is crucial to determine the mechanisms and rates of amyloid formation and replication. In the context of AD, the self-replication of aggregates of the Aβ42 peptide by secondary nucleation, leading to the formation of new aggregates on the surfaces of existing ones, is a major source of both new fibrils and smaller toxic oligomeric species. However, the core mechanistic determinants, including the presence of intermediates, as well as the role of heterogeneities in the fibril population, are challenging to determine from bulk aggregation measurements. Here, we obtain such information by monitoring directly the time evolution of individual fibrils by TIRF microscopy. Crucially, essentially all aggregates have the ability to self-replicate via secondary nucleation, and the amplification of the aggregate concentration cannot be explained by a small fraction of “superspreader” fibrils. We observe that secondary nucleation is a catalytic multistep process involving the attachment of soluble species to the fibril surface, followed by conversion/detachment to yield a new fibril in solution. Furthermore, we find that fibrils formed by secondary nucleation resemble the parent fibril population. This detailed level of mechanistic insights into aggregate self-replication is key in the rational design of potential inhibitors of this process.

Although graphene technology has reached technology readiness level 9 and hydrogen fuel has been identified as a viable futuristic energy resource, pristine atomic layers such as graphene are found to be inactive towards the hydrogen evolution reaction (HER). Enhancing the intrinsic catalytic activity of a material and increasing its number of active sites by nanostructuring are two strategies in novel catalyst development. Here, electrocatalytically inert graphene (G) and hexagonal boron nitride (hBN) are made active for the HER by forming van der Waals (vdW) heterostructures via vertical stacking. The HER studies are conducted using defect free shear exfoliated graphite and hBN modified glassy carbon electrodes via layer by layer sequential stacking. The G/hBN stacking pattern (AA, AB, and AB') and stacking sequence (G/hBN or hBN/G) have been found to play important roles in the HER activity. Enhancement in the intrinsic activity of graphene by the formation of G/hBN vdW stacks has been further confirmed with thermally reduced graphene oxide and hBN based structures. Tunability in the HER performance of the G/hBN vdW stack is also confirmed via a three-dimensional rGO/hBN electrode. HER active sites in the G/hBN vdW structures are then mapped using density functional theory calculations, and an atomistic interpretation has been identified.

Although the interaction of apoE isoforms with amyloid‐β (Aβ) peptides plays a critical role in the progression of Alzheimer's disease, how they interact with each other remains poorly understood. Here, we investigate the molecular mechanism of apoE‐Aβ interactions by comparing the effects of the different domains of apoE on Aβ. The kinetics of aggregation of Aβ1‐42 are delayed dramatically in the presence of substoichiometric, nanomolar concentrations of N‐terminal fragment (NTF), C‐terminal fragment (CTF) and full‐length apoE both in lipid‐free and in lipidated forms. However, interactions between apoE and Aβ as measured by intermolecular Förster resonance energy transfer (FRET) analysis were found to be minimal at t = 0 but to increase in a time‐dependent manner. Thus, apoE must interact with one or more ‘intermediates’ rather than the monomers of Aβ. Kinetics of FRET between full‐length apoE4 labelled with EDANS at position 62 or 139 or 210 or 247 or 276, and tetramethylrhodamine‐labelled Aβ (TMR‐Aβ), further support an involvement of all the three domains of apoE in the interactions. However, the above‐mentioned residues do not appear to form a single pocket in the 3‐dimensional structure of apoE. A competitive binding assay examining the effects of unlabelled fragments or full‐length apoE on the FRET between EDANS‐apoE and TMR‐Aβ show that binding affinity of the full‐length apoE to Aβ is much higher than that of the fragments. Furthermore, apoE4 is found to interact more strongly than apoE3. We hypothesize that high affinity of the apoE‐Aβ interaction is attained due to multivalent binding mediated by multiple interactions between oligomeric Aβ and full‐length apoE.