Phase separation and clustering of an ABC transporter in Mycobacterium tuberculosis

Authors: Florian Heinkel, Libin Abraham, Mary Ko, Joseph D. Chao, Horacio Bach, Lok Tin Hui, Haoran Li, Mang Zhu, Yeou Mei Ling, Jason C. Rogalski, Joshua Scurll, Jennifer M. Bui, Thibault Mayor, Michael R. Gold, Keng C. Chou, Yossef Av‐Gay, Lawrence P. McIntosh, Jörg Gsponer - Proceedings of the National Academy of Sciences, PNAS 2019 cited by 88

Significance Nanoclustering has emerged as an organization principle of membrane proteins. This form of compartmentalization has been observed in eukaryotes and, to a lesser extent, in bacteria. Bacterial membrane proteins in secretion systems often play central roles during host invasion. Here we reveal that an ABC transporter from Mycobacterium tuberculosis ( Mtb ), which is important for its growth in mice, compartmentalizes in the bacterial membrane. We demonstrate that the cytoplasmic region of this transporter has an intrinsic ability to phase-separate into mesoscale assemblies, and that this process is controllable via the action of the signal-integrating serine/threonine protein kinases and phosphatase in Mtb . Our findings suggest that phase separation can play a key role in the regulation of clustering and activity of membrane-bound bacterial proteins.