Periplasmic Binding Protein Dimer Has a Second Allosteric Event Tied to Ligand Binding

Area of Science:

• Biochemistry
• Molecular Biology
• Structural Biology

Background:

• Periplasmic binding proteins (PBP) are essential for metabolite uptake in ATP binding cassette (ABC) transport systems.
• Ligand-induced conformational changes in PBPs regulate metabolite acquisition and transporter recognition.
• Inefficient ATP hydrolysis, uncoupled from transport, remains a challenge in many ABC systems.

Purpose of the Study:

• To identify novel regulatory mechanisms in PBPs that prevent futile ATP hydrolysis.
• To characterize an additional ligand-regulated state of the PBP.
• To elucidate the structural basis for altered PBP-transporter interactions.

Main Methods:

• Structural analysis of periplasmic binding proteins.
• Investigating ligand-induced allosteric regulation.
• Characterizing protein-protein interactions and dynamics.

Main Results:

• A novel, ligand-regulated PBP state was identified.
• Ligand binding induces a conformational shift in PBP interface α-helices.
• This shift alters protein interface contacts and dynamics, favoring a monomeric state.

Conclusions:

• The newly identified PBP state provides an additional layer of regulation beyond conformational change.
• This mechanism enhances the efficiency of ABC transporters by minimizing futile ATP hydrolysis.
• Understanding these structural dynamics is key to optimizing metabolite transport systems.