9G2F

Mouse Teneurin2 dimer variant A1B1

Summary for 9G2F

• Entry DOI: 10.2210/pdb9g2f/pdb
• EMDB information: 50975
• Descriptor: Teneurin transmembrane protein 2, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-3)-beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (5 entities in total)
• Functional Keywords: cell adhesion molecule, complex, homodimer, cell adhesion
• Biological source: Mus musculus (house mouse)
• Total number of polymer chains: 2
• Total formula weight: 543350.29

Authors

Berbeira-Santana, M.,Zhou, J.C.,el Omari, K.,Baker, L.,Seiradake, E. (deposition date: 2024-07-10, release date: 2026-01-21, Last modification date: 2026-08-12)

Primary citation

Berbeira-Santana, M.,Peregrina, C.,Okuda, K.,Zhou, J.C.,Carrasquero-Ordaz, M.,Roberts, A.V.,Thomas, A.E.,Haanappel, E.,Chavent, M.,El Omari, K.,Baker, L.A.,Pederick, D.T.,Pardon, E.,Steyaert, J.,Nagerl, U.V.,Del Toro, D.,Seiradake, E.
Structurally exclusive Teneurin complexes orchestrate divergent programs in early cortical development.
Nat Commun, 17:-, 2026

PubMed Abstract: Cortical migration is a complex process in which neurons migrate along radial glial cells (RGC) to form functional layers. Teneurins (Ten1-4) play a role by interacting with Latrophilins (Lphn/ADGRL1-3). Teneurins are also known as cell adhesion molecules, but how homophilic and heterophilic Teneurin interactions are integrated is unknown. Here, single-particle-cryo-EM data of Ten2 shows that canonical Latrophilin-binding is sterically incompatible with Ten2-dimerisation, making these interactions exclusive. We engineered surface mutations that specifically disrupt Ten2-Ten2 or Ten2-Latrophilin interactions. These are transferrable to Ten4, suggesting conserved binding mechanisms. Proteomics, in-vivo-gene-editing and super-resolution-microscopy show that Ten4 is expressed along RGC fibres and that migrating neurons switch from low-to-high Ten4-expression. Ten4 expression is highest in the cortical plate where Ten4-Ten4 interactions reduce RGC-attachment. In the intermediate zone, Ten4-Latrophilin interactions are required to promote neuron-RGC association. The results show how Ten4 orchestrates different stages of cortical migration by using a structural/functional switch between high-affinity Lphn interactions and low-affinity homophilic interactions, underpinning the integration of distinct migration programmes.

PubMed: 41991904
DOI: 10.1038/s41467-026-71619-1

Experimental method

ELECTRON MICROSCOPY (2.8 Å)