Cripto-1 acts as a molecular bridge linking nodal to ALK4 via distinct structural domains.

ABSTRACT: The TGF-β family ligand Nodal is an essential regulator of embryonic development, orchestrating key processes such as germ layer specification and body axis formation through activation of SMAD2/3-mediated signaling. Significantly, this activation requires the co-receptor Cripto-1. However, despite their essential roles in embryogenesis, the molecular mechanism through which Cripto-1 enables Nodal to activate the SMAD2/3 pathway has remained elusive. Intriguingly, Cripto-1 also has been shown to antagonize other TGF-β family ligands, raising questions about its diverse functions. To clarify how Cripto-1 modulates TGF-β signaling, we integrated AlphaFold3 modeling, surface plasmon resonance (SPR)-based protein-protein interaction analysis, domain-specific anti-Cripto-1 antibodies, and funct

SUBMITTER: Chu KY 

PROVIDER: S-EPMC11751877 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature