Cholesterol transport cycle of human ABCA2
Cholesterol is a key component of cellular membranes and is critical for brain function, particularly axon myelination. Among the 48 human ATP-binding cassette (ABC) transporters, ABCA2 exhibits the highest expression in the brain and is involved in cholesterol metabolism, primarily in oligodendrocytes. Notably, ABCA2 has been associated with myelin sheath integrity and maintenance, as well as…
Cholesterol is vital for proper brain function, especially in terms of axon myelination. Out of 48 human ATP-binding cassette (ABC) transporters, ABCA2 has the highest expression in the brain and plays a significant role in cholesterol metabolism, particularly in oligodendrocytes. Studies have linked ABCA2 to maintaining the integrity and stability of myelin sheaths, as well as its potential connection to Alzheimer's disease.
In this report, researchers have presented cryo-EM structures of human ABCA2, which reveal unique endogenous lipid-binding sites exclusive to ABCA2. These structures showcase five distinct conformations, including a previously unidentified intermediate stage between the closed and apo states typical of ABCA subfamily transporters. Crucially, the study elucidates the cholesterol transport mechanism of ABCA2, which involves the interdependent rotations of the exocytoplasmic domains (ECDs) and regulatory domains (RDs).
This structural insight offers a fresh perspective on the function of ABCA transporters and emphasizes the role of ABCA2 in enabling efficient cholesterol recycling and transport within the brain.
Written by urgent.news from bioRxiv's reporting — not their text. Machine-written — may contain errors; check the original before relying on it.
