Differential Effect of Solution Conditions on the Conformation of the Actinoporins Sticholysin II and Equinatoxin II

Abstract

Actinoporins are a family of pore-forming proteins with hemolytic activity. The structural basis for such activity appears to depend on their correct folding. Such folding encompasses a phosphocholine binding site, a tryptophan-rich region and the activity-related N-terminus segment. Additionally, different solution conditions are known to be able to influence the pore formation by actinoporins, as for Sticholysin II (StnII) and Equinatoxin II (EqtxII). In this context, the current work intends to characterize the influence of distinct solution conditions in the conformational behavior of these proteins through molecular dynamics (MD) simulations. The obtained data offer structural insights into actinoporins dynamics in solution, characterizing its conformational behavior at the atomic level, in accordance with previous experimental data on StnII and EqtxII hemolytic activities.

Functional and Structural Variation among Sticholysins, Pore-Forming Proteins from the Sea Anemone Stichodactyla helianthus

“…However, the specific order of the steps leading to the final pore formation [31,34,128,131,132], the implication of 'pre-pore' structures during the process [31,132,133], and the stoichiometry and detailed pore structure [31,125,126,128,131,134,135], are still controversial. [26,110,124,127,[136][137][138][139]. Upon interaction with a lipid membrane containing SM (b), their N-terminal α-helix stretch is detached and extended, shortly laying parallel to the membrane (c) [25,26,82,85,87,91,116,[140][141][142][143].…”

“…Cartoon schematic representation showing most of the steps generally accepted for the pore formation mechanism of actinoporins. In solution, they remain soluble and stably folded (a)[26,110,124,127,[136][137][138][139]. Upon interaction with a lipid membrane containing SM (b), their N-terminal α-helix stretch is detached and extended, shortly laying parallel to the membrane (c)[25,26,82,85,87,91,116,[140][141][142][143].…”