6KR4

Crystal structure of the liprin-alpha3_SAM123/LAR_D1D2 complex

6KR4 の概要

• エントリーDOI: 10.2210/pdb6kr4/pdb
• 分子名称: Receptor-type tyrosine-protein phosphatase F, Liprin-alpha-3, TETRAETHYLENE GLYCOL, ... (7 entities in total)
• 機能のキーワード: complex, phosphatase, transferase-protein binding complex, transferase/protein binding
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 8
• 化学式量合計: 415722.57

構造登録者

Xie, X.,Liang, M.,Luo, L.,Wei, Z. (登録日: 2019-08-20, 公開日: 2020-01-15, 最終更新日: 2023-11-22)

主引用文献

Xie, X.,Luo, L.,Liang, M.,Zhang, W.,Zhang, T.,Yu, C.,Wei, Z.
Structural basis of liprin-alpha-promoted LAR-RPTP clustering for modulation of phosphatase activity.
Nat Commun, 11:169-169, 2020

PubMed Abstract: Leukocyte common antigen-related receptor protein tyrosine phosphatases (LAR-RPTPs) are cell adhesion molecules involved in mediating neuronal development. The binding of LAR-RPTPs to extracellular ligands induces local clustering of LAR-RPTPs to regulate axon growth and synaptogenesis. LAR-RPTPs interact with synaptic liprin-α proteins via the two cytoplasmic phosphatase domains, D1 and D2. Here we solve the crystal structure of LAR_D1D2 in complex with the SAM repeats of liprin-α3, uncovering a conserved two-site binding mode. Cellular analysis shows that liprin-αs robustly promote clustering of LAR in cells by both the liprin-α/LAR interaction and the oligomerization of liprin-α. Structural analysis reveals a unique homophilic interaction of LAR via the catalytically active D1 domains. Disruption of the D1/D1 interaction diminishes the liprin-α-promoted LAR clustering and increases tyrosine dephosphorylation, demonstrating that the phosphatase activity of LAR is negatively regulated by forming clusters. Additionally, we find that the binding of LAR to liprin-α allosterically regulates the liprin-α/liprin-β interaction.

PubMed: 31924785
DOI: 10.1038/s41467-019-13949-x

実験手法

X-RAY DIFFRACTION (2.85 Å)