BIOPHYSICAL THEORY AND MODELING |
Dynamics and stability of E-cadherin dimers
Fabien Cailliez 1 and Richard Lavery 1*
1 Institut de Biologie Physico-Chimique
* To whom correspondence should be addressed. E-mail: rlavery{at}ibpc.fr.
Submitted on April 14, 2006
Revised on May 17, 2006
Accepted on 24 August 2006
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Abstract |
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The extracellular domains of cadherins are known to play a major role in cell adhesion, although the structures involved in this process remain unclear. We have used molecular dynamics to characterize the conformational and thermodynamic properties of two of the dimer interfaces identified in E-cadherin crystals and involving the two outermost exodomains (EC1 and EC2): a dimer involving exchange of the N-terminal strand (referred to as the "swapped" dimer) and a "staggered" dimer involving an EC1-EC2 interface. The results show that the staggered dimer involves a much smaller interface area and is notably less stable than the swapped dimer. It is also found that, despite its stability, the swapped dimer undergoes a conformational transition leading to a structure closer to that experimentally observed for the homologous C-cadherin. Finally, comparing the simulated dimer structures with the sequences of E-, C- and N- cadherins shows that the swapped dimer interface involves surprisingly few residues which vary from family to family and notably no changes between the E- and C-cadherin exodomains.
Key Words:
Cadherins, Cellular adhesion, Free energy, Molecular dynamics, Selective binding
