Interactions of intrinsically disordered proteins with the unconventional chaperone human serum albumin: From mechanisms of amyloid inhibition to therapeutic opportunities

In Vitro Interaction of a C-Terminal Fragment of TDP-43 Protein with Human Serum Albumin Modulates Its Aggregation

“…The ability of HSA to bind TDP-43 2C was also corroborated by assessing the binding kinetics of TDP-43 2C with HSA using biolayer interferometry, which showed a good binding affinity ( K D ) of ∼0.1 μM. This observation is similar to previous reports that have shown that HSA can bind to α-synuclein oligomers at a sub-micromolar range (0.3 μM), which supported a mechanism of the inhibition of growth of oligomers to large aggregates . Taken together, the data here support that TDP-43 2C interacts with HSA at a sub-micromolar range and retards the in vitro aggregation of TDP-43 2C .…”

“…HSA is also known to interact with intrinsically disordered proteins (IDPs) and prevent their aggregation. Upon interaction, HSA’s inhibitory effects have been reported toward the aggregations of several amyloid proteins such as IDPs like Aβ, α-synuclein, and tau proteins . Owing to the potential of HSA as an amyloid aggregation inhibitor, ,− we have examined here the effect of HSA on the aggregation of a C-terminal fragment of TDP-43 protein, TDP-43 2C , which also harbors an intrinsically disordered C-terminal domain.…”

“…When we analyzed the Thioflavin-T positive species under a fluorescence microscope, the TDP-43 2C alone samples manifested irregularly shaped structures after 60 h of incubation, whereas those in the presence of HSA appeared slow-growing and fewer in numbers. Various mechanisms have been proposed regarding the inhibitory effect of HSA on the aggregation of IDPs . HSA can either prevent the formation of toxic oligomers or prevent the formation of amyloid fibrils.…”

Interaction of Human Resistin with Human Islet Amyloid Polypeptide at Charged Phospholipid Membranes

“…There are some studies about the inhibition of hIAPP aggregation by natural products, their derivatives, 11 , 24 , 25 and molecular crowders, 26 but there are few studies on the interaction of protein chaperones with hIAPP. 2 , 27 , 28 This paper focuses on the interaction of human resistin with human IAPP at anionic phospholipid model membranes. We show that human resistin inhibited the oligomerization of hIAPP at the membrane.…”

“…However, human resistin also undergoes conformational changes, which result in β-sheet structures comparable with those in pathophysiological conditions of prion proteins. , Resistin was postulated to be the missing key molecule in the relationship between obesity and diabetes. − Investigations on the polypeptide level in interaction with hIAPP are lacking. There are some studies about the inhibition of hIAPP aggregation by natural products, their derivatives, ,, and molecular crowders, but there are few studies on the interaction of protein chaperones with hIAPP. ,, This paper focuses on the interaction of human resistin with human IAPP at anionic phospholipid model membranes. We show that human resistin inhibited the oligomerization of hIAPP at the membrane.…”