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

Le Li; Sudipa Ghimire-Rijal; Sarah L. Lucas; Christopher B. Stanley; Edward Wright; Pratul K. Agarwal; Dean A. Myles; Matthew J. Cuneo

doi:10.1021/acs.biochem.7b00657

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

Le Li, Sudipa Ghimire-Rijal, Sarah L. Lucas, Christopher B. Stanley, Edward Wright, Pratul K. Agarwal, Dean A. Myles, Matthew J. Cuneo

Research output: Contribution to journal › Article › peer-review

13 Scopus citations

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.

Original language	English
Pages (from-to)	5328-5337
Number of pages	10
Journal	Biochemistry
Volume	56
Issue number	40
DOIs	https://doi.org/10.1021/acs.biochem.7b00657
State	Published - Oct 10 2017

Funding

The Oak Ridge National Laboratory Center for Structural Molecular Biology (FWP ERKP291) is supported by the Office of Biological and Environmental Research of the U.S. Department of Energy. Research at the Spallation Neutron Source of Oak Ridge National Laboratory was sponsored by the Scientific User Facilities Division, Office of Basic Energy Sciences, U.S. Department of Energy. The authors would like to thank X. Lu for help with crystallographic data. P.K.A. was supported by a grant from NIH (GM105978).

Funders	Funder number
Office of Basic Energy Sciences
Office of Biological and Environmental Research
Scientific User Facilities Division
National Institutes of Health
U.S. Department of Energy
National Institute of General Medical Sciences	R01GM105978
Oak Ridge National Laboratory	FWP ERKP291

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10.1021/acs.biochem.7b00657

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title = "Periplasmic Binding Protein Dimer Has a Second Allosteric Event Tied to Ligand Binding",

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.",

author = "Le Li and Sudipa Ghimire-Rijal and Lucas, {Sarah L.} and Stanley, {Christopher B.} and Edward Wright and Agarwal, {Pratul K.} and Myles, {Dean A.} and Cuneo, {Matthew J.}",

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T1 - Periplasmic Binding Protein Dimer Has a Second Allosteric Event Tied to Ligand Binding

AU - Li, Le

AU - Ghimire-Rijal, Sudipa

AU - Lucas, Sarah L.

AU - Stanley, Christopher B.

AU - Wright, Edward

AU - Agarwal, Pratul K.

AU - Myles, Dean A.

AU - Cuneo, Matthew J.

PY - 2017/10/10

Y1 - 2017/10/10

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AB - 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.

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ER -

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

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