Structural modelling of the extracellular domains of the E-cadherin protein.

<p>In A–B PyMOL and Coot softwares representations of EC1–EC2 protomers based on human sequence (PDB code: 2O72); in C–F, EC3 and EC4 protomers based on murine E-cadherin (PDB code: 3Q2W) by Coot software. (A) Cartoon representation highlights A144 (<i>yellow</i>) position: A144 is near to calcium sites (<i>purple</i>) and in proximity of the dimerization interface between EC1 (<i>blue</i>)-EC2 (<i>green</i>) domains. (B) Structural representation of A144T substitution in EC2 domain. Position of AT144 is spotlighted in yellow. Threonine in position 144 is quite dramatic for local structure because it interacts with two Aspartic acid residues (<i>green</i>) directly involved in calcium sites, and these bond lengths are particularly stressed being less than 3 Å. (C) The T316 (<i>yellow</i>) is <i>O</i>-glycosilated (<i>blue</i>) and present on the surface of EC3 domain. (D) The hydrophobic lateral chain of I316 (<i>yellow</i>) cannot be <i>O</i>-glycosilated and promotes protein-protein interactions. (E) The methylenic side chain of A438 (<i>yellow</i>) allows conformational freedom on the surface of EC4 domain. (F) T438 (<i>yellow</i>) substitution is not dramatic for local structure but it could represent a potential site for post-translational modifications. Calcium ions are highlighted (<i>green</i>).