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

Biochemistry. 2017 Oct 10;56(40):5328-5337. doi: 10.1021/acs.biochem.7b00657. Epub 2017 Sep 22.

Abstract

The ligand-induced conformational changes of periplasmic binding proteins (PBP) play a key role in the acquisition of metabolites in ATP binding cassette (ABC) transport systems. This conformational change allows for differential recognition of the ligand occupancy of the PBP by the ABC transporter. This minimizes futile ATP hydrolysis in the transporter, a phenomenon in which ATP hydrolysis is not coupled to metabolite transport. In many systems, the PBP conformational change is insufficient at eliminating futile ATP hydrolysis. Here we identify an additional state of the PBP that is also allosterically regulated by the ligand. Ligand binding to the homodimeric apo PBP leads to a tightening of the interface α-helices so that the hydrogen bonding pattern shifts to that of a 310 helix, in-turn altering the contacts and the dynamics of the protein interface so that the monomer exists in the presence of ligand.

MeSH terms

  • ATP-Binding Cassette Transporters / metabolism
  • Adenosine Triphosphate / metabolism
  • Allosteric Regulation
  • Amino Acid Sequence
  • Apoproteins / chemistry
  • Apoproteins / metabolism
  • Bacterial Proteins / chemistry*
  • Bacterial Proteins / metabolism*
  • Crystallography, X-Ray
  • Hydrolysis
  • Ligands
  • Mannose-Binding Lectin / chemistry
  • Mannose-Binding Lectin / metabolism
  • Models, Molecular
  • Periplasmic Binding Proteins / chemistry*
  • Periplasmic Binding Proteins / metabolism*
  • Protein Binding
  • Protein Multimerization*
  • Protein Structure, Quaternary
  • Thermotoga maritima

Substances

  • ATP-Binding Cassette Transporters
  • Apoproteins
  • Bacterial Proteins
  • Ligands
  • Mannose-Binding Lectin
  • Periplasmic Binding Proteins
  • Adenosine Triphosphate