Structural biases in disordered proteins are prevalent in the cell

Area of Science:

• Biochemistry
• Molecular Biology
• Structural Biology

Background:

• Intrinsically disordered proteins (IDPs) lack stable 3D structures but possess functional significance.
• IDPs exist as dynamic ensembles of conformations, influenced by intramolecular interactions.
• The in-cell structural biases of IDPs remain largely uncharacterized.

Purpose of the Study:

• To determine if in vitro structural biases of IDPs are maintained within living cells.
• To investigate how cellular factors influence IDP structural ensembles.
• To explore the functional implications of IDP structural plasticity in vivo.

Main Methods:

• Utilized biophysical techniques to characterize IDP ensembles in vitro and in human cells.
• Investigated sequence-dependent structural changes in response to varying intracellular conditions.
• Examined the impact of subcellular localization and interactions with folded domains on IDP structures.

Main Results:

• Confirmed that IDP structural biases observed in vitro are recapitulated within human cells.
• Demonstrated that intracellular milieu, localization, and interactions modulate IDP ensemble structures.
• Showed sequence-specific alterations in IDP structural biases due to cellular context.

Conclusions:

• IDP structural ensembles are stable and functionally relevant within the cellular environment.
• Cellular context dynamically regulates IDP structure, impacting their function.
• IDP structural sensitivity presents opportunities for designing novel biosensors and understanding disease mechanisms.