ABCA1 - ATP Binding Cassette Transporter A1 |Elisa - Clia - Antibody - Protein

Background

ATP-binding cassette transporters form a superfamily of transport systems, representing one of the largest and potentially oldest gene families, spanning from prokaryotes to humans. ABC transporters typically comprise multiple subunits, with one or two acting as transmembrane proteins and one or two as membrane-associated ATPases. The ATPase subunits utilize energy derived from adenosine triphosphate (ATP) hydrolysis to facilitate the transport of various substrates across membranes. These transported substances include ions, amino acids, peptides, sugars, and predominantly hydrophilic molecules. Exporters function as pumps, expelling toxins and drugs from the cell. In gram-negative bacteria, exporters play a crucial role in transporting lipids and specific polysaccharides across membranes. Eukaryotes lack importers, and exporters are found in both prokaryotes and eukaryotes. The versatility of ABC transporters underscores their essential role in cellular transport processes across diverse organisms.The ABCA subfamily, consisting of 12 members to date, exhibits a high degree of sequence conservation and is primarily associated with lipid trafficking in various body locations. Mutations in some of these genes have been linked to severe hereditary diseases related to lipid transport, such as fatal surfactant deficiency or harlequin ichthyosis. Additionally, many ABCA subfamily members are hypothesized to participate in the subcellular sequestration of drugs, contributing to the resistance of several carcinoma cell lines against drug treatment.

Structural Features

ABCA Transporters share common structural features typical of ABC transporters:

•  Transmembrane Domains (TMDs): Composed of multiple membrane-spanning alpha-helices that form the pathway through which substrates are transported.
• Nucleotide-Binding Domains (NBDs): Sites where ATP binding and hydrolysis occur, providing the energy required for substrate transport.
• Regulatory Regions: Additional domains and motifs that may regulate transporter activity, localization, and interaction with other cellular components.
• Subtypes and Classification

 ABCA1

• Function: ABCA1 is crucial for the efflux of cholesterol and phospholipids to apolipoproteins, which are then converted into high-density lipoprotein (HDL). This process is essential for reverse cholesterol transport, a pathway that removes excess cholesterol from peripheral tissues to the liver for excretion.
• Clinical Relevance: Mutations in ABCA1 can lead to Tangier disease and familial HDL deficiency, both characterized by extremely low levels of HDL cholesterol and an increased risk of cardiovascular disease.

Ligands and Interactions

• The primary ligands and substrates for ABCA transporters include:
• Cholesterol and Phospholipids: Particularly for ABCA1, which facilitates their efflux to HDL.
• Retinoids: For ABCA4 in the visual cycle.
• Lipid Metabolites: General for other ABCA transporters involved in lipid metabolism.
• ATP: Binding and hydrolysis of ATP at the NBDs provide the energy for substrate transport.

Physiological Functions

 ABCA transporters are involved in several critical physiological functions:

• Lipid Homeostasis: Maintaining balance and proper distribution of lipids within cells and tissues.
• Cholesterol Efflux: Removing excess cholesterol from cells, crucial for cardiovascular health.
• Surfactant Production: Essential for lung function and prevention of respiratory distress.
• Visual Cycle: Involved in the processing of visual pigments in the retina.

Clinical Implications

Dysfunction or mutations in ABCA transporters can lead to a variety of diseases:

• Cardiovascular Diseases: Related to ABCA1 mutations leading to impaired cholesterol efflux.
• Neurodegenerative Diseases: Potential involvement of ABCA2 in disorders like Alzheimer's disease.
• Respiratory Diseases: ABCA3 mutations causing neonatal respiratory distress and lung disease.
• Retinal Degeneration: ABCA4 mutations leading to vision loss in Stargardt disease.