Multiscale Simulations Reveal Dynamics Interfacial Network and Membrane Remodeling of the Ankyrin-1 Complex

Area of Science:

• Biophysics
• Cell Biology
• Structural Biology

Background:

• The ankyrin-1 complex links the cytoskeleton to the plasma membrane, maintaining cell mechanical integrity.
• High-resolution structures exist, but the dynamic behavior of its interfaces is poorly understood.

Purpose of the Study:

• To investigate the dynamic behavior of ankyrin-1 complex interfaces using multiscale molecular dynamics simulations.
• To understand the molecular mechanisms of ankyrin-1 complex stability and membrane anchoring.

Main Methods:

• Multiscale molecular dynamics simulations (all-atom and coarse-grained) of the ankyrin-1 complex in a lipid bilayer.
• Quantification of binding affinities for five key interfaces (AP, PB-I, AB-II, AB-III, AR).
• Identification of hotspot residues critical for interfacial stability.

Main Results:

• All five key interfaces exhibit metastable substates with dynamic rearrangements, indicating intrinsic structural plasticity.
• The ankyrin-1 complex induces significant lipid reorganization and a unique "valley"-like membrane deformation.
• Global membrane convexity and localized outer leaflet indentation optimize membrane embedding.

Conclusions:

• Provides a comprehensive molecular understanding of ankyrin-1 complex interface dynamics and membrane anchoring.
• Elucidates the cytoskeleton-membrane coupling essential for cellular mechanical integrity.
• Highlights the role of dynamic structural plasticity in complex stability and function.