α-Synuclein is a presynaptic protein associated to Parkinson’s disease, which is unstructured when free in the cytoplasm and adopts α helical conformation when bound to vesicles. After decades of intense studies, α-Synuclein physiology is still difficult to clear up due to its interaction with multiple partners and its involvement in apletoraof neuronal functions. Here, we looked at the remarkably neglected interplay between α-Synuclein and microtubules, which potentially impacts on synaptic functionality. In order to identify the mechanisms underlying these actions, we investigated the interaction between purified α-Synuclein and tubulin. We demonstrated that α-Synuclein binds to microtubules and tubulin α₂β₂tetramer; the latter interaction inducing the formation of helical segment(s) in the α-Synuclein polypeptide. This structural change seems to enable α-Synuclein to promote microtubule nucleation and to enhance microtubule growth rate and catastrophe frequency, bothin vitroandin cell. We also showed that Parkinson’s disease-linked α-Synuclein variants do not undergo tubulin-induced folding and cause tubulin aggregation rather than polymerization. Our data enable us to propose α-Synuclein as a novel, foldable, microtubule-dynamase, which influences microtubule organisation through its binding to tubulin and its regulating effects on microtubule nucleation and dynamics.

Long-life excimer-like structures: Metal quantum clusters have ideal properties for medical applications such as imaging. The challenge is to prolong their transient properties for the fabrication of useful devices. Santiago-Gonzalez et al. arranged gold clusters in a supramolecular lattice held together by hydrogen bonding and showed that this material can be used for imaging of fibroblast cells. In the superstructure, the gold molecules can come together in the excited state as excimers and then dissociate to emit radiation. Because they are within a lattice, this behavior shows long-term stability. Furthermore, the lattice superstructure scavenges reactive oxygen species and reduces cell damage. Science , this issue p. 571

β2 microglobulin (β2m) is the light chain of class‐I major histocompatibility complex (MHC‐I). Its accumulation in the blood of patients affected by kidney failure leads to amyloid deposition around skeletal joints and bones, a severe condition known as Dialysis Related Amyloidosis (DRA). In an effort to dissect the structural determinants of β2m aggregation, several β2m mutants have been previously studied. Among these, three single‐residue mutations in the loop connecting strands D and E (W60G, W60V, D59P) have been shown to affect β2m amyloidogenic properties, and are here considered. To investigate the biochemical and biophysical properties of wild‐type (w.t.) β2m and the three mutants, we explored thermal unfolding by Trp fluorescence and circular dichroism (CD). The W60G mutant reveals a pronounced increase in conformational stability. Protein oligomerization and reduction kinetics were investigated by electrospray‐ionization mass spectrometry (ESI‐MS). All the mutations analyzed here reduce the protein propensity to form soluble oligomers, suggesting a role for the DE‐loop in intermolecular interactions. A partially folded intermediate, which may be involved in protein aggregation induced by acids, accumulates for all the tested proteins at pH 2.5 under oxidizing conditions. Moreover, the kinetics of disulfide reduction reveals specific differences among the tested mutants. Thus, β2m DE‐loop mutations display long‐range effects, affecting stability and structural properties of the native protein and its low‐pH intermediate. The evidence presented here hints to a crucial role played by the DE‐loop in determining the overall properties of native and partially folded β2m.