ABC transporter

Overview

Structure of an ABC transporter protein.

ATP-binding cassette (ABC) transporters are a large family of proteins that utilize the energy derived from ATP hydrolysis to transport various substrates across cellular membranes. These transporters are found in all domains of life, including bacteria, archaea, and eukaryotes. They play critical roles in processes such as nutrient uptake, toxin secretion, and drug resistance.

Structure

Crystal structure of an ABC transporter.

ABC transporters are characterized by their highly conserved ATP-binding domains, also known as nucleotide-binding domains (NBDs), and transmembrane domains (TMDs) that form the pathway for substrate transport. The NBDs are responsible for binding and hydrolyzing ATP, which provides the energy required for the transport process.

Nucleotide-Binding Domains

The NBDs of ABC transporters contain several conserved motifs, including the Walker A and Walker B motifs, which are essential for ATP binding and hydrolysis. These domains are highly conserved across different species, reflecting their fundamental role in the transport mechanism.

Transmembrane Domains

The TMDs are composed of multiple alpha-helices that span the membrane. These domains determine the specificity of the transporter for its substrate and form the translocation pathway through which the substrate is moved across the membrane.

Function

ABC transporter in action.

ABC transporters are involved in the transport of a wide variety of substrates, including ions, sugars, lipids, peptides, and proteins. They can function as importers or exporters, depending on the direction of transport relative to the cell.

Importers

In prokaryotes, ABC transporters often function as importers, facilitating the uptake of essential nutrients such as amino acids, sugars, and metal ions. These transporters typically work in conjunction with substrate-binding proteins that deliver the substrate to the transporter.

Exporters

In both prokaryotes and eukaryotes, ABC transporters can function as exporters, removing toxic compounds, drugs, and metabolic waste products from the cell. This function is particularly important in the context of multidrug resistance, where ABC transporters can expel a wide range of drugs, reducing their efficacy.

Mechanism

Mechanism of substrate transport by an ABC transporter.

The transport cycle of an ABC transporter involves several key steps:

1. Substrate Binding: The substrate binds to the transporter, often with the help of a substrate-binding protein in the case of importers. 2. ATP Binding: ATP molecules bind to the NBDs, inducing a conformational change in the transporter. 3. Substrate Translocation: The conformational change opens the translocation pathway, allowing the substrate to move across the membrane. 4. ATP Hydrolysis: Hydrolysis of ATP to ADP and inorganic phosphate provides the energy for the conformational change. 5. Resetting: The transporter returns to its original state, ready for another cycle.

Clinical Significance

File:Abc-sav.jpg

ABC transporter involved in drug resistance.

ABC transporters are clinically significant due to their role in multidrug resistance (MDR) in cancer and infectious diseases. Overexpression of certain ABC transporters in cancer cells can lead to the efflux of chemotherapeutic drugs, rendering treatment less effective. Similarly, in bacteria, ABC transporters can contribute to antibiotic resistance.

Related Pages

• Membrane transport protein
• ATP hydrolysis
• Multidrug resistance
• Nucleotide-binding domain