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Chemical Modification of the Tryptophan Residue in a Recombinant Ca2+-ATPase N-domain for Studying Tryptophan-ANS FRET
Published on: October 9, 2021
Insights into how nucleotide-binding domains power ABC transport
Simon Newstead1, Philip W Fowler, Paul Bilton
1Division of Molecular Biosciences, Membrane Protein Crystallography Group, Imperial College London, London, UK.
Structure (London, England : 1993)
|September 15, 2009
Summary
The mechanism of ABC transporters remains unclear. This study reveals that nucleotide-binding domains (NBDs) like FbpC rapidly open upon ATP removal, driven by their free energy, powering substrate transport.
Area of Science:
- Structural biology
- Biochemistry
- Molecular dynamics
Background:
- The precise mechanism by which nucleotide-binding domains (NBDs) of ATP-binding cassette (ABC) transporters generate energy for substrate translocation across membranes is not fully understood.
- ABC transporters are crucial for various cellular processes, including nutrient uptake and toxin efflux.
Purpose of the Study:
- To elucidate the structural and dynamic mechanisms underlying the energy transduction in ABC transporters.
- To investigate the role of domain swapping in the NBD FbpC from Neisseria gonorrhoeae ferric iron transporter.
Main Methods:
- X-ray crystallography was used to determine the structure of FbpC.
- Molecular dynamics simulations were employed to study the conformational changes and energetics of NBDs.
Main Results:
- A crystal structure of FbpC revealed an unusual domain swap in its C-terminal regulatory domain.
- Molecular dynamics simulations demonstrated that both FbpC and MalK NBDs open rapidly after ATP hydrolysis.
- The closed states of FbpC and MalK possess higher free energies compared to their open states.
Conclusions:
- The rapid opening of NBDs upon ATP removal is powered by the release of free energy stored in the closed conformation.
- This energy release mechanism is critical for understanding power generation in ABC transporters.
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