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

Cytokinesis of animal and fungi cells depends crucially on the anillin scaffold proteins. Fission yeast anillin-related Mid1 anchors cytokinetic ring precursor nodes to the membrane. However, it is unclear if both of its Pleckstrin Homology (PH) and C2 C-terminal domains bind to the membrane as monomers or dimers, and if one domain plays a dominant role. We studied Mid1 membrane binding with all-atom molecular dynamics near a membrane with yeast-like lipid composition. In simulations with the full C terminal region started away from the membrane, Mid1 binds through the disordered L3 loop of C2 in a vertical orientation, with the PH away from the membrane. However, a configuration with both C2 and PH initially bound to the membrane remains associated with the membrane. Simulations of C2-PH dimers show extensive asymmetric membrane contacts. These multiple modes of binding may reflect Mid1’s multiple interactions with membranes, node proteins, and ability to sustain mechanical forces. [Display omitted] •Molecular dynamics simulation of anillin-related Mid1 binding to yeast-like membrane•Initially unbound C-terminal region establishes contacts through L3 loop of C2 domain•Evidence for PH domain membrane binding and membrane insertion of NLS region of L3 loop•Simulations indicate multiple modes of Mid1 binding to membrane as monomer or dimer Hall et al. used all-atom molecular dynamics simulations to study protein Mid1, which anchors cytokinetic nodes to the plasma membrane during fission yeast cytokinesis. Mid1 diffuses and binds to a yeast-like membrane through its disordered L3 loop. Monomers and dimers can develop additional contacts, indicating its adaptive and multimodal anchoring.