Molecular Dynamics Simulation Reveals Unique Interplays Between a Tarantula Toxin and Lipid Membranes

Area of Science:

• Biochemistry
• Molecular Biology
• Biophysics

Background:

• Tarantula toxins are a significant class of spider toxins targeting ion channels.
• Some toxins are known to interact with lipid membranes, influencing their function.
• Jingzhaotoxin-III (JZTx-III) specifically targets the cardiac voltage-gated sodium channel Na[Formula: see text]1.5 and may interact with lipid membranes.

Purpose of the Study:

• To investigate the interactions between JZTx-III and lipid membranes of varying compositions using computational methods.
• To understand how JZTx-III binding affects membrane structure and dynamics.
• To elucidate the role of lipid-membrane interactions in JZTx-III's specific binding to Na[Formula: see text]1.5.

Main Methods:

• All-atom molecular dynamics simulations.
• Long-term simulations to analyze toxin-membrane interactions.
• Trajectory analysis and sequence alignment.

Main Results:

• JZTx-III shows no significant interaction with neutral 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) lipids.
• JZTx-III binds to membranes containing negatively charged 1-palmitoyl-2-oleoyl-sn-glycero-3-[phospho-rac-(1-glycerol)] (POPG) lipids.
• Binding to POPC/POPG mixed membranes induces a phase transition to a rippled phase, unlike pure POPG membranes.
• JZTx-III binding causes minor conformational changes in both mixed and pure POPG membranes.
• Sequence analysis suggests JZTx-III may not fully partition into the lipid bilayer due to specific residue mutations.

Conclusions:

• JZTx-III exhibits distinct interactions with different lipid membrane compositions.
• The observed toxin-membrane interactions, including membrane phase transitions and conformational changes, may contribute to JZTx-III's specific binding to Na[Formula: see text]1.5.
• This study enhances the understanding of complex interactions between spider toxins and lipid membranes.