In a recent study published in the journal Nature Communications , researchers structurally analyzed adenine nucleotide control and neurodegenerative diseases in ClC-3 exchangers. Study: Structural basis of adenine nucleotides regulation and neurodegenerative pathology in ClC-3 exchanger . Image Credit: Lightspring / Shutterstock ClC-3, a chloride/proton exchanger, is necessary for monitoring metabolic energy levels and is activated by adenosine triphosphate (ATP).
Point-type mutations in the ClC-3 ion channels can cause neurological disorders in humans. The cause of these mutations' gain of function remains unclear. ClC-3, ClC-4, and ClC-5 are metabolic energy sensors that aid in acidification and divert vacuolar-type ATPase (V-ATPase) electrical current.
Knockout animals have severe retinal degeneration and aberrant protein breakdown. Two disease-causing ClC-3 variants in humans, T570I and I607T generate higher current amplitudes at negatively charged transmembrane voltages, although the mechanism is unknown. About the study In the present study, researchers obtained high-resolution dimeric wild-type murine ClC-3 structures in apo states and combined them with adenosine monophosphate (AMP), adenosine diphosphate (ADP), and ATP.
They also investigated the I607T mutation in apo and ATP-bound forms. The researchers used cryogenic electron microscopy to identify ClC-3 structures under different circumstances, verifying the functional s.