skip to main content
OSTI.GOV title logo U.S. Department of Energy
Office of Scientific and Technical Information

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

Abstract

Here, 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 alpha-helices so that the hydrogen bonding pattern shifts to that of a 3 10 helix, in-turn altering the contacts and the dynamics of the protein interface so that the monomer exists in the presence of ligand.

Authors:
ORCiD logo [1];  [1];  [2]; ORCiD logo [1];  [3]; ORCiD logo [4];  [1]; ORCiD logo [1]
  1. Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)
  2. Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); North Carolina State Univ., Raleigh, NC (United States)
  3. Univ. of Tennessee, Knoxville, TN (United States)
  4. Univ. of Tennessee, Knoxville, TN (United States); Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)
Publication Date:
Research Org.:
Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)
Sponsoring Org.:
USDOE
OSTI Identifier:
1407759
Grant/Contract Number:
AC05-00OR22725
Resource Type:
Journal Article: Accepted Manuscript
Journal Name:
Biochemistry
Additional Journal Information:
Journal Volume: 56; Journal Issue: 40; Journal ID: ISSN 0006-2960
Publisher:
American Chemical Society (ACS)
Country of Publication:
United States
Language:
English
Subject:
37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY; 59 BASIC BIOLOGICAL SCIENCES

Citation Formats

Li, Le, Ghimire-Rijal, Sudipa, Lucas, Sarah L., Stanley, Christopher B., Wright, Edward, Agarwal, Pratul K., Myles, Dean A., and Cuneo, Matthew J.. Periplasmic Binding Protein Dimer Has a Second Allosteric Event Tied to Ligand Binding. United States: N. p., 2017. Web. doi:10.1021/acs.biochem.7b00657.
Li, Le, Ghimire-Rijal, Sudipa, Lucas, Sarah L., Stanley, Christopher B., Wright, Edward, Agarwal, Pratul K., Myles, Dean A., & Cuneo, Matthew J.. Periplasmic Binding Protein Dimer Has a Second Allosteric Event Tied to Ligand Binding. United States. doi:10.1021/acs.biochem.7b00657.
Li, Le, Ghimire-Rijal, Sudipa, Lucas, Sarah L., Stanley, Christopher B., Wright, Edward, Agarwal, Pratul K., Myles, Dean A., and Cuneo, Matthew J.. Wed . "Periplasmic Binding Protein Dimer Has a Second Allosteric Event Tied to Ligand Binding". United States. doi:10.1021/acs.biochem.7b00657.
@article{osti_1407759,
title = {Periplasmic Binding Protein Dimer Has a Second Allosteric Event Tied to Ligand Binding},
author = {Li, Le and Ghimire-Rijal, Sudipa and Lucas, Sarah L. and Stanley, Christopher B. and Wright, Edward and Agarwal, Pratul K. and Myles, Dean A. and Cuneo, Matthew J.},
abstractNote = {Here, 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 alpha-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.},
doi = {10.1021/acs.biochem.7b00657},
journal = {Biochemistry},
number = 40,
volume = 56,
place = {United States},
year = {Wed Sep 06 00:00:00 EDT 2017},
month = {Wed Sep 06 00:00:00 EDT 2017}
}

Journal Article:
Free Publicly Available Full Text
This content will become publicly available on September 6, 2018
Publisher's Version of Record

Save / Share: