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A Step-by-step Method for the Reconstitution of an ABC Transporter into Nanodisc Lipid Particles
Published on: August 31, 2012
Structure and function of ABC transporters
1MRC Clinical Sciences Centre, Imperial College Hammersmith Hospital Campus, London, United Kingdom. kenneth.linton@csc.mrc.ac.uk
Abstract:
ATP binding cassette transporters are ubiquitous integral membrane proteins that actively transport ligands across biological membranes, a process critical for most aspects of cell physiology. These proteins are important clinically and economically. Their dysfunction underlies a number of human genetic diseases, and the ability of some to pump cytotoxic molecules from cells confers resistance to antibiotics, herbicides, and chemotherapeutic drugs. Recent structure analyses interpreted in light of a large body of biochemistry has resulted in the ATP-switch model for function in which the paired nucleotide binding domains switch between an ATP-dependent closed conformation and a nucleotide-free, open conformation to drive the translocation of ligand.
Insights
ATP binding cassette transporters are vital integral membrane proteins. Recent studies reveal their function through an ATP-switch model, crucial for cell physiology and disease.
Area of Science:
- Biochemistry
- Molecular Biology
- Cell Physiology
Background:
- ATP binding cassette transporters are ubiquitous integral membrane proteins.
- These transporters are critical for cell physiology, with clinical and economic importance.
- Dysfunction is linked to genetic diseases and drug resistance.
Purpose of the Study:
- To elucidate the functional mechanism of ATP binding cassette transporters.
- To integrate structural and biochemical data for a comprehensive understanding.
- To explain ligand translocation across biological membranes.
Main Methods:
- Recent structure analyses of ATP binding cassette transporters.
- Interpretation of structural data in the context of extensive biochemical studies.
- Development of a functional model based on integrated data.
Main Results:
- The ATP-switch model for transporter function has been proposed.
- The model involves paired nucleotide binding domains switching conformations.
- Conformational changes are dependent on ATP binding and hydrolysis.
Conclusions:
- The ATP-switch model explains how ATP binding cassette transporters translocate ligands.
- This model highlights the dynamic nature of these integral membrane proteins.
- Understanding this mechanism is key to addressing related diseases and drug resistance.
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