Solvation driven conformational transitions in the second transmembrane domain of mycobacteriophage holin

Abstract

Holins are pore-forming membrane proteins synthesized by lytic phages. The second transmembrane domain (TM2) of Mycobacteriophage D29 holin presents an Ala- and Gly-rich sequence, with a currently unknown structure and function. In this study, we present the spectroscopic characterization of synthetic TM2 in various solvents, detergents, and lipids. We find that TM2 adopts α-helical conformation under conditions that promote intra-strand hydrogen bonding, such as organic solvents and detergent micelles. When we transfer the peptide to a well-hydrated environment, a polyproline II-like structure is obtained. Surprisingly, we find that the polyproline II–like conformation is retained in lipid vesicles. Based on our results, we present a putative role for TM2 in the process of pore formation by holin.