Figure 4. The C‐rich region is a calcium‐binding domain and linker.

• A
  Sequence alignment of the C‐rich region, including disulfide bonds as brackets, calcium‐coordinating acidic residues in red and domain interface residues in green. The consensus symbols are according to Clustal Omega. Pink box highlights the C‐rich domain in the four human Teneurins.
• B
  The Teneurin4 dimer with one chain colored grey in cartoon and transparent surface representation, and the other chain colored according to Fig 1C with the C‐rich domain and C‐rich linker in cartoon representation and all other domains in surface representation. Region shown in C indicated with dashed box.
• C
  The C‐rich domain and C‐rich linker straddle the TTR domain, colored purple in surface representation. The calcium ions are shown in green. Coloring as in B. C‐rich domain shown in D indicated with dashed box.
• D
  C‐rich domain in cartoon representation with disulfide bonds in stick representation and labeled. Calcium ions are represented by green spheres.
• E
  Stick representation and 2mF_obs‐DF_calc electron density map at 1σ level of the C‐rich domain showing that three calcium ions (I–III) are each ligated in octahedral coordination. Calcium‐coordinating residues are labeled.
• F, G
  Thermal shift assay traces of human Teneurin4^WT (F) and human Teneurin4^Mut (G) in the presence of physiological calcium concentrations (+ Ca²⁺; black), low calcium concentration (+/− Ca²⁺; blue and red, respectively) and no calcium (− Ca²⁺; grey).

Data information: Data are represented as mean ± SEM. Each condition was performed in triplicates.