| Autor: |
Jackson VA; Department of Biochemistry, Oxford University, OX1 3QU, Oxford, UK. verity.jackson@magd.ox.ac.uk., Meijer DH; Crystal and Structural Chemistry, Bijvoet Center for Biomolecular Research, Faculty of Science, Utrecht University, 3584 CH, Utrecht, The Netherlands., Carrasquero M; Department of Biochemistry, Oxford University, OX1 3QU, Oxford, UK., van Bezouwen LS; Crystal and Structural Chemistry, Bijvoet Center for Biomolecular Research, Faculty of Science, Utrecht University, 3584 CH, Utrecht, The Netherlands.; Cryo-electron Microscopy, Bijvoet Center for Biomolecular Research, Faculty of Science, Utrecht University, 3584 CH, Utrecht, The Netherlands., Lowe ED; Department of Biochemistry, Oxford University, OX1 3QU, Oxford, UK., Kleanthous C; Department of Biochemistry, Oxford University, OX1 3QU, Oxford, UK., Janssen BJC; Crystal and Structural Chemistry, Bijvoet Center for Biomolecular Research, Faculty of Science, Utrecht University, 3584 CH, Utrecht, The Netherlands., Seiradake E; Department of Biochemistry, Oxford University, OX1 3QU, Oxford, UK. elena.seiradake@bioch.ox.ac.uk. |
| Abstrakt: |
Teneurins are ancient cell-cell adhesion receptors that are vital for brain development and synapse organisation. They originated in early metazoan evolution through a horizontal gene transfer event when a bacterial YD-repeat toxin fused to a eukaryotic receptor. We present X-ray crystallography and cryo-EM structures of two Teneurins, revealing a ~200 kDa extracellular super-fold in which eight sub-domains form an intricate structure centred on a spiralling YD-repeat shell. An alternatively spliced loop, which is implicated in homophilic Teneurin interaction and specificity, is exposed and thus poised for interaction. The N-terminal side of the shell is 'plugged' via a fibronectin-plug domain combination, which defines a new class of YD proteins. Unexpectedly, we find that these proteins are widespread amongst modern bacteria, suggesting early metazoan receptor evolution from a distinct class of proteins, which today includes both bacterial proteins and eukaryotic Teneurins. |
