The 3K5S T-cadherin is attached peripherally to the cell surface, via a GPI anchor, having no inner membrane or cytoplasmic domain, shortening the total weight and length of a single unit, hence the name truncated. (Ranscht B, Dours-Zimmermann MT. T-cadherin, a novel cadherin cell adhesion molecule in the nervous system, lacks the conserved cytoplasmic region. Neuron. 1991 Sep;7(3):391-402. doi: 10.1016/0896-6273(91)90291-7. PMID: 1654948.) This binding method and reduced size benefit 3K5S in its role of aiding neurite development and signaling in chick growth. The soft structure and shorter signalling reach allows for a more fluid and less tense growth environment for neural development. The concentration of 3K5S is slowly diminished as other cadherins, because more necessary for adult synaptic maintenance. (https://www.sciencedirect.com/science/article/pii/S0006899308002813#:~:text=Three%20types%20of%20full%2Dlength%20cDNAs%20encoding%20chicken,high%20similarity%20to%20rat%20and%20human%20Cdh8.)
Structural Highlights
The crystal structure 3K5S (2.90 Å resolution) encompasses two extracellular cadherin domains (EC1 and EC2) of chick T-cadherin forming a symmetric X-shaped dimer, contacting each other at the center of the cross. The individual extracellular units consist of 2 β-barrel sections separated by the interdomain area of hydrophobic residues (Met198, Val203, Leu205) where the Ca 2+ ligand ions and to the other extracellular unit are bound to. The truncated C terminus is visible at the bottom of each unit, pointing towards the cell the EC is attached to, this is where the intermembrane domain would have protruded from in a classical cadherin. Instead, the anchoring method is added post-translationally in the form of a GPI anchor made to fit the C-terminus region where a hydrophobic sequence of amino acids directs the attachment of the GPI anchor.
Each EC has three Ca 2+ binding sites that collectively hold a hydrophobic charge that drives much of the interaction and bond strength between the EC units, these residues include Asp140, Asp99, and Glu142. These regions are also some of the most conserved of the sequence likely due to their pivotal role in the adhesion between EC1 and EC2. In addition to the driving force of the ligands and the hydrophobic pocket there are a hand full of cross domain H-bonds between residues that act to consolidate the structure further around areas around the EC cross site. Ex. Arg104xAsp20
Disease Relevance
Disruption in T-cadherin concentrations or structures can lead to numerous neurological disorders and increased chick mortality rates. Abnormally functioning T-cadherins can cause improper neural development that could cascade into issues such as overexcited neurons, motor control deficiencies, hormone imbalances, and disease susceptibility.
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