Structural dynamics of IDR interactions in human SFPQ and implications for liquid-liquid phase separation

Area of Science:

• Biochemistry and Molecular Biology
• Structural Biology

Background:

• SFPQ and NONO are DBHS proteins crucial for gene regulation.
• Their intrinsically disordered regions (IDRs) are vital for function but difficult to study.
• IDRs influence protein interactions, cellular processes, and disease.

Purpose of the Study:

• To structurally characterize the disordered regions of SFPQ.
• To investigate SFPQ's dimer partner exchange capabilities.

Main Methods:

• Small-angle X-ray scattering (SAXS) and Small-angle neutron scattering (SANS).
• Lysine cross-linking mass spectrometry (XL-MS).

Main Results:

• SFPQ's N- and C-terminal regions are long, disordered, and flexible.
• IDRs can interact in cis or trans, potentially with the DBHS domain.
• Full-length SFPQ undergoes dynamic dimer partner exchange.

Conclusions:

• Disordered regions of SFPQ are structurally dynamic and capable of interaction.
• Dimer partner exchange is a key mechanism for DBHS protein function in gene regulation.