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Abstract
Response mechanisms to external stress rely on networks of proteins able to activate specific signaling pathways to ensure the maintenance of cell proteostasis. Many of the proteins mediating this kind of response contain intrinsically disordered regions, which lack a defined structure, but still are able to interact with a wide range of clients that modulate the protein function. Some of these interactions are mediated by specific short sequences embedded in the longer disordered regions. Because the physicochemical properties that promote functional and abnormal interactions are similar, it has been shown that, in globular proteins, aggregation-prone and binding regions tend to overlap. It could be that the same principle applies for disordered protein regions. In this context, we show here that a predicted low-complexity interacting region in the disordered C-terminus of the stress response master regulator heat shock factor 1 (Hsf1) protein corresponds to a cryptic amyloid region able to self-assemble into fibrillary structures resembling those found in neurodegenerative disorders.
Highlights
Eukaryotic cells have the capacity to overcome detrimental environmental conditions, such as hyperthermia or oxidative stress
It is shown here that, in yeast heat shock factor 1 (Hsf1), a disordered and low complexity region at the C-terminus of this transcription factor is predicted to act in molecular recognition, at the cost of aggregating spontaneously into ordered amyloid assemblies
PFAM indicates that yeast Hsf1 contains a single annotated functional domain comprising residues 175–275, which correspond to the HSF_DNA-binding domain [21]
Summary
Eukaryotic cells have the capacity to overcome detrimental environmental conditions, such as hyperthermia or oxidative stress. Despite the fact that the DBD corresponds to a folded domain, Hsf is thought to be mostly unstructured [7] It is well-established that numerous proteins related with DNA-binding and transcriptional regulation lack ordered tertiary structure or contain long disordered segments under physiological conditions [8,9]. In these proteins, disordered regions contribute to their conformational plasticity and client promiscuity and this is crucial to establish a wide range of specific interactions [10]. It is shown here that, in yeast Hsf, a disordered and low complexity region at the C-terminus of this transcription factor is predicted to act in molecular recognition, at the cost of aggregating spontaneously into ordered amyloid assemblies
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