Dataset curation & revision: Maria Victoria Nugnes
Curators: Ximena Aixa Castro, Rita Pancsa, Erzsébet Fichó, Jaime Santos Suárez, Bernadett Juhász, Gabriel Alejandro Rivas

How do cells survive stress?

Living organisms are constantly exposed to stressful conditions such as heat shock, oxidative stress, nutrient starvation, dehydration, and many other environmental challenges. To survive, cells change and activate mechanisms that protect proteins, restore cellular balance, and adapt to the new conditions.

Intrinsically disordered proteins (IDPs) and intrinsically disordered regions (IDRs) play an important role in these processes. With the latest DisProt thematic dataset, we focus on stress response proteins and highlight how intrinsic disorder contributes to cellular adaptation in different organisms and biological systems.

The dataset includes proteins involved in heat shock responses, stress signaling, transcriptional regulation, protein quality control, and environmental adaptation. Together, these proteins show that intrinsic disorder is a conserved strategy used by cells to respond to stress across evolution.

Overview of the dataset

• 142 curated proteins
• 2629 different organisms
• 176 curated publications
• Proteins involved in heat shock response, oxidative stress, integrated stress response, and plant stress adaptation

Examples of disordered stress-response proteins

Protein name: Heat shock protein beta-6

DisProt ID: DP01131
Organism: Homo sapiens

Heat Shock Protein Beta-6 (HSPB6) is a small heat shock protein that helps cells maintain protein homeostasis during stress. DisProt annotates IDRs that undergo a disorder-to-order transition when HSPB6 binds its partners. Structural evidence from SAXS and X-ray crystallography shows that these flexible regions become structured during complex formation.

The newly curated functional annotations show that IDRs mediate self-interaction, which is important for oligomer formation, and 14-3-3 protein binding, an interaction involved in stress-related signaling pathways.

Protein name: NAC domain-containing protein 13

DisProt ID: DP03136
Organism: Arabidopsis thaliana

NAC013 is a membrane-associated transcription factor involved in the response to mitochondrial and oxidative stress in plants. DisProt contains experimental evidence about disorder structural annotations, disorder-to-order transitions, and a pre-molten globule state, showing the high structural flexibility of its regulatory regions.

These regions are also annotated with several functions, including protein binding, self-assembly, and transcription regulator activator activity.

Protein name: Protein Phosphatase 1 Regulatory Subunit 15A

DisProt ID: DP01203
Organism: Homo sapiens

PPP1R15A, also known as GADD34, is an important regulator of the Integrated Stress Response (ISR), a conserved pathway that helps cells recover from different types of stress. DisProt annotates the full-length protein as intrinsically disordered, highlighting how structural flexibility is essential for its function.

Its disordered regions mediate Protein Phosphatase 1 (PP1) binding, eukaryotic initiation factor eIF2 binding, and protein phosphatase regulator activity. These interactions are required to assemble the PP1 regulatory complex, which restores protein synthesis after stress and helps cells return to normal conditions.