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

Autor: Meijer DH; Department of Bionanoscience, Kavli Institute of Nanoscience, Delft University of Technology, Delft, The Netherlands.; Department of Chemistry, Faculty of Science, Structural Biochemistry, Bijvoet Center for Biomolecular Research, Utrecht University, Utrecht, The Netherlands., Frias CP; Department of Bionanoscience, Kavli Institute of Nanoscience, Delft University of Technology, Delft, The Netherlands., Beugelink JW; Department of Chemistry, Faculty of Science, Structural Biochemistry, Bijvoet Center for Biomolecular Research, Utrecht University, Utrecht, The Netherlands., Deurloo YN; Department of Bionanoscience, Kavli Institute of Nanoscience, Delft University of Technology, Delft, The Netherlands., Janssen BJC; Department of Chemistry, Faculty of Science, Structural Biochemistry, Bijvoet Center for Biomolecular Research, Utrecht University, Utrecht, The Netherlands.
Jazyk: angličtina
Zdroj: The EMBO journal [EMBO J] 2022 May 02; Vol. 41 (9), pp. e107505. Date of Electronic Publication: 2022 Jan 31.
DOI: 10.15252/embj.2020107505
Abstrakt: 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.
(© 2022 The Authors. Published under the terms of the CC BY 4.0 license.)
Databáze: MEDLINE
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