Structural basis of liprin-α-promoted LAR-RPTP clustering for modulation of phosphatase activity.

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.

SUBMITTER: Xie X 

PROVIDER: S-EPMC6954185 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature