Molecular dynamics simulations reveal that apo-HisJ can sample a closed conformation
B C H Chu1, D I Chan, T DeWolf
1Department of Biological Sciences, University of Calgary, Calgary, Alberta T2N 1N4, Canada.
Proteins
|August 23, 2013
Summary
The Escherichia coli histidine binding protein HisJ can adopt a closed conformation even without histidine bound. This finding explains how unliganded proteins interact with their transporters, facilitating histidine import.
Area of Science:
- Biochemistry
- Structural Biology
- Molecular Dynamics
Background:
- Escherichia coli histidine binding protein HisJ is a type II periplasmic binding protein (PBP).
- HisJ binds histidine and interacts with the HisQMP2 ABC transporter for histidine transport.
- Type II PBPs exhibit 'Venus flytrap' movements, transitioning between open and closed states.
Purpose of the Study:
- To investigate the accessibility of the closed conformation in the apo (unliganded) state of HisJ.
- To understand the dynamics and conformational changes of HisJ.
Main Methods:
- All-atom molecular dynamics simulations of HisJ.
- Simulations initiated from four distinct conformations: apo-open, apo-closed, apo-semiopen, and holo-closed.
- Essential dynamics analysis to identify key protein motions.
Main Results:
- The closed conformation of HisJ is less dynamic than the open conformation.
- HisJ explored semiopen conformations that reverted to closed states, similar to the holo-closed state.
- Domain closing/opening and twisting were identified as primary motions, driven by inter-hinge strand and interdomain polar interactions.
Conclusions:
- Apo-HisJ can sample closed conformations, providing a mechanism for interaction with cytoplasmic membrane ABC transporters.
- This sampling explains the binding of unliganded PBPs to their transporters, initiating substrate uptake.
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