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Teneurin4 dimer structures reveal a calcium‐stabilized compact conformation supporting homomeric trans‐interactions

DOI: 10.15252/embj.2020107505 DOI Help

Authors: Dimphna H Meijer (Delft University of Technology; Utrecht University) , Cátia P Frias (Delft University of Technology) , J. Wouter Beugelink (Utrecht University) , Yanthi N. Deurloo (Delft University of Technology) , Bert J. C. Janssen (Utrecht University)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: The Embo Journal , VOL 66

State: Published (Approved)
Published: January 2022
Diamond Proposal Number(s): 19800

Open Access Open Access

Abstract: Establishment of correct synaptic connections is a crucial step during neural circuitry formation. The Teneurin family of neuronal transmembrane proteins promotes cell–cell adhesion via homophilic and heterophilic interactions, and is required for synaptic partner matching in the visual and hippocampal systems in vertebrates. It remains unclear how individual Teneurins form macromolecular cis- and trans-synaptic protein complexes. Here, we present a 2.7 Å cryo-EM structure of the dimeric ectodomain of human Teneurin4. The structure reveals a compact conformation of the dimer, stabilized by interactions mediated by the C-rich, YD-shell, and ABD domains. A 1.5 Å crystal structure of the C-rich domain shows three conserved calcium binding sites, and thermal unfolding assays and SAXS-based rigid-body modeling demonstrate that the compactness and stability of Teneurin4 dimers are calcium-dependent. Teneurin4 dimers form a more extended conformation in conditions that lack calcium. Cellular assays reveal that the compact cis-dimer is compatible with homomeric trans-interactions. Together, these findings support a role for teneurins as a scaffold for macromolecular complex assembly and the establishment of cis- and trans-synaptic interactions to construct functional neuronal circuits.

Journal Keywords: neuroscience; structural biology; synaptic cell adhesion; Teneurins; transmembrane proteins

Subject Areas: Biology and Bio-materials

Instruments: B21-High Throughput SAXS

Other Facilities: ID23-1 at ESRF

Added On: 01/02/2022 13:11

The EMBO Journal - 2022 - Meijer - Teneurin4 dimer structures reveal a calcium%E2%80%90stabilized compact conformation supporting.pdf

Discipline Tags:

Health & Wellbeing Neurology Structural biology Life Sciences & Biotech

Technical Tags:

Scattering Small Angle X-ray Scattering (SAXS)