Protein induced membrane phase transition facilitates leishmania infection

Abstract

AbstractAlthough host membrane is known to play critical roles in the internalization of leishmania parasites inside macrophages (Mϕ), any detailed mechanistic understanding is missing. We show here that KMP-11, a small immunogenic protein ofLeishmania Donovani(LD) facilitates the infection process by binding to Mϕ membrane through its N-terminal domain (1-19AA). This binding results in a membrane phase transition that occurs at a threshold protein/lipid ratio, which is linked to the change in membrane tension. KMP-11 induced phase transition is also associated with lipid raft disruption and T-cell deactivation. Finally, using a combination of tryptophan-scanning mutagenesis and synthesized peptides, we develop a mathematical exposition, which demonstrates that hydrophobic moment (μH) and the number of residues involved in a mirror sequence (N) at the interacting N-terminal are governing factors for the membrane phase transition, which facilitates infection process.