8SUF

The complex of TOL-1 ectodomain bound to LAT-1 Lectin domain

Summary for 8SUF

• Entry DOI: 10.2210/pdb8suf/pdb
• Descriptor: TIR domain-containing protein, Latrophilin-like protein 1, alpha-D-mannopyranose-(1-6)-beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (8 entities in total)
• Functional Keywords: cell surface receptor, cell adhesion
• Biological source: Caenorhabditis elegans; More
• Total number of polymer chains: 8
• Total formula weight: 507337.26

Authors

Carmona Rosas, G.,Li, J.,Arac, D.,Ozkan, E. (deposition date: 2023-05-12, release date: 2024-05-15, Last modification date: 2025-11-26)

Primary citation

Carmona-Rosas, G.,Li, J.,Smith, J.J.,Nawrocka, W.I.,Cheng, S.,Baltrusaitis, E.E.,Zhao, M.,Arac, D.,Kratsios, P.,Ozkan, E.
Structural basis and functional roles for Toll-like receptor binding to Latrophilin in C. elegans development.
Nat.Struct.Mol.Biol., 32:1683-1696, 2025

PubMed Abstract: Latrophilins are conserved adhesion-type G-protein-coupled receptors associated with embryonic defects and lethality. However, their mechanistic roles and ligands in embryogenesis remain unknown. Here, we identified TOL-1, the sole Toll-like receptor in Caenorhabditis elegans, as a ligand for the C. elegans latrophilin, LAT-1. The extracellular lectin domain of LAT-1 directly binds to the second leucine-rich repeat domain of TOL-1. The crystal structure and cryo-electron microscopy density map of the LAT-1-TOL-1 extracellular region complex reveal a one-to-one lectin domain interaction with the convex face of a leucine-rich repeat domain. In C. elegans, endogenous mRNA and protein localization analyses showed mutually exclusive sites of expression, suggesting that in vivo LAT-1-TOL-1 interactions mostly occur in trans. Mutagenesis of key interface residues that disrupt the LAT-1-TOL-1 interaction led to partial lethality and malformed embryos. Thus, TOL-1 binding to LAT-1 represents a receptor-ligand axis essential for animal development.

PubMed: 40588662
DOI: 10.1038/s41594-025-01592-8

Experimental method

X-RAY DIFFRACTION (4 Å)