Capturing the Membrane-Triggered Conformational Transition of an alpha-Helical Pore-Forming Toxin

Rao, Hemanth Giri V V and Desikan, Rajat and Ayappa, Ganapathy K and Gosavi, Shachi (2016) Capturing the Membrane-Triggered Conformational Transition of an alpha-Helical Pore-Forming Toxin. In: JOURNAL OF PHYSICAL CHEMISTRY B, 120 (47). pp. 12064-12078.

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Abstract

Escherichia coli cytolysin A (ClyA) is an alpha-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 beta-tongue inserts first while the insertion of helix alpha A1 is membrane assisted. We conclude that the beta-tongue is designed to behave as a quick-response membrane sensor, while helix alpha A1 improves target selectivity for cholesterol-containing cell membranes by acting as a fidelity check.

Item Type:	Journal Article
Publication:	JOURNAL OF PHYSICAL CHEMISTRY B
Publisher:	AMER CHEMICAL SOC, 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
Additional Information:	Copy right for this article belongs to the AMER CHEMICAL SOC, 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
Department/Centre:	Division of Mechanical Sciences > Chemical Engineering
Date Deposited:	04 Jan 2017 05:27
Last Modified:	26 Oct 2018 07:34
URI:	http://eprints.iisc.ac.in/id/eprint/55853

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