
@article {11604,
	title = {Capturing the Membrane-Triggered Conformational Transition of an α-Helical Pore-Forming Toxin.},
	journal = {J Phys Chem B},
	volume = {120},
	year = {2016},
	month = {2016 Dec 01},
	pages = {12064-12078},
	abstract = {<p>Escherichia coli cytolysin A (ClyA) is an α-helical pore-forming toxin (PFT) which lyses target cells by forming membrane permeabilizing pores. The rate-determining step of this process is the conversion of the soluble ClyA monomer into a membrane inserted protomer. We elucidate the mechanism of this conformational transition using molecular dynamics simulations of coarse-grained models of ClyA and a membrane. We find that a membrane is necessary for the conformational conversion because membrane-protein interactions counteract the loss of the many intraprotein hydrophobic interactions that stabilize the membrane-inserting segments in the ClyA monomer. Of the two membrane-inserting segments, the flexible and highly hydrophobic β-tongue inserts first while the insertion of helix αA1 is membrane assisted. We conclude that the β-tongue is designed to behave as a quick-response membrane sensor, while helix αA1 improves target selectivity for cholesterol-containing cell membranes by acting as a fidelity check.</p>
},
	issn = {1520-5207},
	doi = {10.1021/acs.jpcb.6b09400},
	author = {Giri Rao, V V Hemanth and Desikan, Rajat and Ayappa, K Ganapathy and Gosavi, Shachi}
}
