Protein induced membrane phase transition facilitates leishmania infection
Sannigrahi, A.; Jawed, J. J.; Majumdar, S.; Roy, S.; Karmakar, S.; Chattopadhyay, K.
Show abstract
Although host membrane is known to play critical roles in the internalization of leishmania parasites inside macrophages (M{phi}), any detailed mechanistic understanding is missing. We show here that KMP-11, a small immunogenic protein of Leishmania Donovani (LD) facilitates the infection process by binding to M{phi} 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 (H) 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.
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