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Tom1 Modulates Binding of Tollip to Phosphatidylinositol 3-Phosphate via a Coupled Folding and Binding Mechanism •Tollip TBD is a disordered domain that partially folds when bound to Tom1 GAT •Tom1 GAT also directly binds to the Tollip C2 domain •Binding of Tom1 to Tollip inhibits binding of Tollip to PtdIns(3)P •Tollip TBD plays a major role in Tom1’s inhibitory function

It has important implications for Rx of allergies, heart disease, cancer types. The discovery explains how 2 particular proteins, Tollip and Tom1, work together to contribute to the turnover of cell-surface receptor proteins that trigger inflammation...

It could lead to the development of new drugs to treat the disease. The study found that the protein fragment, sAPPα, inhibits the proteolytic enzyme BACE1. Increased BACE1 activity contributes to production of the amyloid beta aggregates and plaques that are the hallmark of Alzheimer’s.

“Because sAPPα inhibits the BACE1 enzyme, it may be possible that it can be used to help prevent potentially dangerous increases in BACE1 activity, and thus prevent the onset of Alzheimer’s disease,” A/Prof Varghese John.

The protein fragment sAPPa is normally produced by neurons and is involved in maintenance of memory...