Multiple dimeric structures and strand-swap dimerization of E-cadherin in solution visualized by high-speed atomic...

Area of Science:

• Cell Biology
• Biophysics
• Structural Biology

Background:

• Classical cadherins are crucial for cell-cell adhesion.
• Cadherin dimerization, involving X-dimer and strand-swap (SS-) dimer formation, is central to adhesion.
• Previous studies faced limitations in visualizing dynamic cadherin binding processes.

Purpose of the Study:

• To investigate the dynamic binding process of cadherin dimerization.
• To identify novel dimeric structures and binding states of E-cadherin ectodomains.
• To elucidate the sequential steps in cadherin dimerization.

Main Methods:

• High-speed atomic force microscopy (HS-AFM) to observe full-length E-cadherin ectodomains in solution.
• Mutational analysis to probe binding interfaces.
• Molecular modeling to complement experimental findings.

Main Results:

• Identification of multiple, previously unreported dimeric structures of E-cadherin ectodomains.
• Observation of dynamic S-shaped (or reverse S-) cadherin dimers, distinct from X- and SS-dimers.
• Direct visualization of SS-dimer formation from S-shaped and X-like dimers.

Conclusions:

• Cadherin dimerization involves more complex binding states than previously thought.
• S-shaped dimers represent a novel, dynamic intermediate in the cadherin dimerization pathway.
• HS-AFM provides unprecedented insights into the dynamic mechanisms of cadherin-mediated adhesion.