ATP-driven dynamics and itraconazole binding of the drug efflux pump Cdr1 from Candida glabrata.

Cryo-EM structures reveal ATP-driven conformational changes in Candida glabrata Cdr1 that facilitate drug efflux and itraconazole binding.

• Why it matters: Understanding the structural basis of Cdr1's function is crucial because its overexpression causes azole resistance in Candida species, impacting clinical treatment options.
• What they did: Four high-resolution cryo-EM structures of Cdr1 were obtained in different nucleotide and substrate states, complemented by 3D variability analysis to observe structural transitions linked to ATP hydrolysis.
• The result: The study uncovers a piston-like motion of the C-helix and conformational shifts in transmembrane helices that enable drug binding and extrusion, providing a framework for understanding azole resistance mechanisms.