Computational insights into intrinsically disordered regions in protein-nucleic acid complexes

Area of Science:

• Structural Biology
• Biochemistry
• Molecular Biology

Background:

• Intrinsically disordered regions (IDRs) are protein segments lacking stable 3D structures in isolation.
• IDRs play critical roles in various biological processes, including molecular recognition and complex formation.
• Understanding IDR behavior upon binding to other molecules, like nucleic acids, is key to deciphering their function.

Purpose of the Study:

• To investigate the structural transitions of intrinsically disordered regions (IDRs) when proteins form complexes with DNA and RNA.
• To classify these transitions and analyze the interactions of IDRs at the protein-nucleic acid interface.

Main Methods:

• Utilized an X-ray-solved structural dataset of protein-DNA and protein-RNA complexes.
• Compared structures of bound complexes with their available unbound protein forms to identify IDR transitions.
• Categorized IDRs into Disordered-to-Ordered (D-O), Disordered-to-Partial Ordered (D-PO), and Disordered-to-Disordered (D-D) classes.

Main Results:

• Observed three types of IDR transitions: D-O, D-PO, and D-D.
• In the D-O class, IDRs formed secondary structures (coils, helices, strands) upon nucleic acid binding.
• Interface IDRs (B_IDRs) formed more hydrogen bonds with nucleic acid phosphates than sugars, with preferential interactions with ribose (RNA) over deoxyribose (DNA). Arg and Lys residues targeted major/minor grooves, while Ser preferred the minor groove.

Conclusions:

• IDRs undergo significant structural changes upon protein-nucleic acid complex formation, often adopting ordered structures.
• Specific amino acid residues within IDRs mediate critical interactions within the grooves of DNA and RNA.
• The study identified numerous IDRs involved in these transitions, suggesting that nucleic acid binding can also induce ordered-to-disordered transitions in proteins.