A protein thermal sensing mechanism for newly characterized stress-specific amyloid body recruitment

Amyloid aggregates are an extraordinarily damage resistant protein structure. Although they've traditionally been thought of as an inherently toxic protein state, cells can in fact utilize amyloid aggregation in various ways. In conditions of extreme cell stress, the formation of subnuclear, reversible amyloid like compartments, called A-bodies, promotes survival by inducing a dormant cell state. The extent of the biological consequences of A-body formation is still not clear but considering ~200 proteins have been identified as potential A-body pathway targets, those effects are likely extremely diverse and wide ranging. This work shows that recruitment to A-bodies is stimulus dependent, with some proteins being targeted in a stress specific manner, while others are universal targets. It is also demonstrated that manipulating the structural stability of A-body proteins can either induce or restrict their targeting during heat stress. A mechanistic model is proposed where selective aggregation within A-bodies is regulated by intrinsic protein stability, with different structural motifs acting as stress-sensing switches that expose or conceal A-body targeting sequences. This system could act as a potent, inherent post-translational regulation mechanism that allows proteins to quickly and reversibly modulate their activity and be protected from damage by forming physiological amyloids, in a context appropriate manner, by virtue of their evolved native levels of stability.