7PLP

Human Teneurin-4 C-rich domain

7PLP の概要

• エントリーDOI: 10.2210/pdb7plp/pdb
• 分子名称: Teneurin-4, CALCIUM ION, FE (III) ION, ... (6 entities in total)
• 機能のキーワード: cysteine-rich, calcium binding, cell adhesion
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 10852.64

構造登録者

Beugelink, J.W.,Meijer, D.H.,Janssen, B.J.C. (登録日: 2021-09-01, 公開日: 2022-02-02, 最終更新日: 2024-11-13)

主引用文献

Meijer, D.H.,Frias, C.P.,Beugelink, J.W.,Deurloo, Y.N.,Janssen, B.J.C.
Teneurin4 dimer structures reveal a calcium-stabilized compact conformation supporting homomeric trans-interactions.
Embo J., 41:e107505-e107505, 2022

PubMed 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.

PubMed: 35099835
DOI: 10.15252/embj.2020107505

実験手法

X-RAY DIFFRACTION (1.4 Å)