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The protein vitellogenin (Vg) plays a central role in lipid transportation in most egg‐laying animals. High Vg levels correlate with stress resistance and lifespan potential in honey bees (Apis mellifera). Vg is the primary circulating zinc‐carrying protein in honey bees. Zinc is an essential metal ion in numerous biological processes, including the function and structure of many proteins. Measurements of Zn2+ suggest a variable number of ions per Vg molecule in different animal species, but the molecular implications of zinc‐binding by this protein are not well‐understood. We used inductively coupled plasma mass spectrometry to determine that, on average, each honey bee Vg molecule binds 3 Zn2+‐ions. Our full‐length protein structure and sequence analysis revealed seven potential zinc‐binding sites. These are located in the β‐barrel and α‐helical subdomains of the N‐terminal domain, the lipid binding site, and the cysteine‐rich C‐terminal region of unknown function. Interestingly, two potential zinc‐binding sites in the β‐barrel can support a proposed role for this structure in DNA‐binding. Overall, our findings suggest that honey bee Vg bind zinc at several functional regions, indicating that Zn2+‐ions are important for many of the activities of this protein. In addition to being potentially relevant for other egg‐laying species, these insights provide a platform for studies of metal ions in bee health, which is of global interest due to recent declines in pollinator numbers. [ABSTRACT FROM AUTHOR]

Dysregulation of the biosynthesis of cholesterol and other lipids has been implicated in many neurological diseases, including Parkinson's disease. Misfolding of α‐synuclein (α‐Syn), the main actor in Parkinson's disease, is associated with changes in a lipid environment. However, the exact molecular mechanisms underlying cholesterol effect on α‐Syn binding to lipids as well as α‐Syn oligomerization and fibrillation remain elusive, as does the relative importance of cholesterol compared to other factors. We probed the interactions and fibrillation behaviour of α‐Syn using styrene–maleic acid nanodiscs, containing zwitterionic and anionic lipid model systems with and without cholesterol. Surface plasmon resonance and thioflavin T fluorescence assays were employed to monitor α‐Syn binding, as well as fibrillation in the absence and presence of membrane models. 1H‐15N‐correlated NMR was used to monitor the fold of α‐Syn in response to nanodisc binding, determining individual residue apparent affinities for the nanodisc‐contained bilayers. The addition of cholesterol inhibited α‐Syn interaction with lipid bilayers and, however, significantly promoted α‐Syn fibrillation, with a more than a 20‐fold reduction of lag times before fibrillation onset. When α‐Syn bilayer interactions were analysed at an individual residue level by solution‐state NMR, we observed two different effects of cholesterol. In nanodiscs made of DOPC, the addition of cholesterol modulated the NAC part of α‐Syn, leading to stronger interaction of this region with the lipid bilayer. In contrast, in the nanodiscs comprising DOPC, DOPE and DOPG, the NAC part was mostly unaffected by the presence of cholesterol, while the binding of the N and the C termini was both inhibited. [ABSTRACT FROM AUTHOR]