Anillin-related Mid1 as an adaptive and multimodal contractile ring anchoring protein: A simulation study

Area of Science:

• Cell biology
• Molecular biology
• Biophysics

Background:

• Anillin scaffold proteins are essential for cytokinesis in animal and fungi cells.
• Fission yeast anillin-related Mid1 protein anchors cytokinetic ring precursor nodes to the membrane.
• The membrane-binding mechanism of Mid1's Pleckstrin Homology (PH) and C2 domains (monomer vs. dimer, dominant domain) remains unclear.

Purpose of the Study:

• To investigate the membrane binding modes of fission yeast Mid1.
• To determine if Mid1's PH and C2 domains bind as monomers or dimers.
• To elucidate the role of each domain in membrane association.

Main Methods:

• All-atom molecular dynamics simulations.
• Simulations conducted near a membrane with a yeast-like lipid composition.
• Analysis of Mid1 binding orientations and interactions with the membrane.

Main Results:

• Mid1 binds the membrane via the C2 domain's L3 loop in a vertical orientation when starting away from the membrane, with the PH domain oriented away.
• A configuration where both C2 and PH domains initially bind the membrane results in sustained association.
• Simulations of C2-PH dimers demonstrate extensive asymmetric membrane contacts.

Conclusions:

• Mid1 exhibits multiple binding modes to membranes, involving different domains and orientations.
• These diverse binding strategies likely facilitate Mid1's interactions with membranes, node proteins, and its ability to withstand mechanical forces during cytokinesis.