13.8
ABC Transporters: Exporter
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Q1: What are the structural components of ABC transporters?
ABC transporters contain two transmembrane domains that span the lipid bilayer and two cytoplasmic nucleotide-binding or ATP-binding domains. The transmembrane domains are specific to their substrates, while the nucleotide-binding domains function like engines that complete ATP hydrolysis to drive substrate transport across the membrane.
Q2: How does an ABC exporter move solutes across the cell membrane?
An ABC exporter begins in an inward-facing conformation with the solute-binding site exposed to the cytosol. When a cytosolic solute binds, it increases ATP affinity. ATP binding triggers a conformational change to outward-facing, releasing the solute into extracellular space. ATP hydrolysis then reverts the transporter to its initial inward-facing state.
Q3: Why are ABC transporters found differently in prokaryotes versus eukaryotes?
Eukaryotic ABC transporters function only as exporters of solutes. In contrast, bacteria have both ABC importers and exporters, and some plants also possess importers. This difference reflects evolutionary adaptations to distinct cellular transport needs and membrane organization between prokaryotic and eukaryotic organisms.
Q4: What role does ABCB1 play in drug resistance during cancer treatment?
ABCB1, also called P-glycoprotein 1, transports natural and metabolic toxins out of cells. During evolution, it acquired the ability to transport drugs with structures similar to endogenous toxins. This causes significant drug resistance by preventing intracellular accumulation of anti-cancer drugs and reducing treatment efficacy.
Q5: How do ABC transporters contribute to chloroquine resistance in malaria parasites?
Plasmodium falciparum, the parasite causing malaria, develops chloroquine resistance through mutations in the PfMDR1 transporter. This multidrug resistance protein reduces intracellular drug concentration, allowing the parasite to survive treatment. This resistance emerges over time as the parasite population adapts to the drug.
Q6: How many ABC transporter genes exist in humans and how are they classified?
Humans have 49 known ABC genes classified into seven families. These transporters represent the largest superfamily of integral membrane proteins. Each family contains transporters with distinct substrate specificities and cellular functions, reflecting the diversity of transport requirements in human cells.
Q7: What types of ABC transporter structures exist beyond full transporters?
ABC transporters include full transporters with two transmembrane domains and nucleotide-binding domains, half transporters with one of each domain, and single-domain structures encoded with either one transmembrane domain or one nucleotide-binding domain. This structural diversity allows cells to employ various transport mechanisms suited to different physiological requirements.