@article{WOS:000661116600003, abstract = {``Pink″ or 1/f noise is a natural phenomenon omnipresent in physics, economics, astrophysics, biology, and even music and languages. In electrophysiology, the stochastic activity of a number of biological ion channels and artificial nanopores could be characterized by current noise with a 1/f power spectral density. In the anthrax toxin channel (PA(63)), it appears as fast voltage-independent current interruptions between conducting and nonconducting states. This behavior hampers potential development of PA(63) as an ion-channel biosensor. On the bright side, the PA(63) flickering represents a mesmerizing phenomenon to investigate. Notably, similar 1/f fluctuations are observed in the channel-forming components of clostridial binary C2 and iota toxins, which share functional and structural similarities with the anthrax toxin channel. Similar to PA(63), they are evolved to translocate the enzymatic components of the toxins into the cytosol. Here, using high-resolution single-channel lipid bilayer experiments and all-atom molecular dynamic simulations, we suggest that the 1/f noise in PA(63) occurs as a result of ``hydrophobic gating″ at the phi-clamp region, the phenomenon earlier observed in several water-filled channels ``fastened″ inside by the hydrophobic belts. The phi-clamp is a narrow ``hydrophobic ring″ in the PA(63) lumen formed by seven or eight phenylalanine residues at position 427, conserved in the C2 and iota toxin channels, which catalyzes protein translocation. Notably, the 1/f noise remains undetected in the F427A PA(63) mutant. This finding can elucidate the functional purpose of 1/f noise and its possible role in the transport of the enzymatic components of binary toxins.}, author = {Yamini, Goli and Kanchi, Subbarao and Kalu, Nnanya and Abolfath, Sanaz Momben and Leppla, Stephen H. and Ayappa, K. Ganapathy and Maiti, Prabal K. and Nestorovich, Ekaterina M.}, doi = {10.1021/acs.jpcb.0c10490}, eissn = {1520-5207}, issn = {1520-6106}, journal = {JOURNAL OF PHYSICAL CHEMISTRY B}, month = {JUN 3}, number = {21}, orcid-numbers = {Maiti, Prabal K/0000-0002-9956-1136 Kanchi, Subbarao/0000-0001-9147-0101}, pages = {5466-5478}, title = {Hydrophobic Gating and 1/f Noise of the Anthrax Toxin Channel}, unique-id = {WOS:000661116600003}, volume = {125}, year = {2021} }