Structures of Teneurin adhesion receptors reveal an ancient fold for cell-cell interaction

Journal article

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.

Authors: Jackson, V; Meijer, D; Carrasquero, M; van Bezouwen, L; Lowe, E

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Macmillan
• Journal: Nature Communications
• Volume: 9
• Issue: 1
• Article number: 1079
• Publication date: 2018-03-14
• Acceptance date: 2018-02-13
• DOI: 10.1038/s41467-018-03460-0
• ISSN: 2041-1723
• Pmid: 29540701
• Language: English
• Keywords: membrane Glycoproteins; protein structure, secondary; Tenascin; platelet Glycoprotein GPIb-IX complex; Crystallography, X-Ray; alternative splicing; cell communication; Cryoelectron microscopy