Structural basis for the recognition of two consecutive mutually interacting DPF motifs by the SGIP1 ? homology domain.

ABSTRACT: FCHo1, FCHo2, and SGIP1 are key regulators of clathrin-mediated endocytosis. Their ? homology domains (?HDs) interact with the C-terminal region of an endocytic scaffold protein, Eps15, containing fifteen Asp-Pro-Phe (DPF) motifs. Here, we show that the high-affinity ?HD-binding site in Eps15 is a region encompassing six consecutive DPF motifs, while the minimal ?HD-binding unit is two consecutive DPF motifs. We present the crystal structures of the SGIP1??HD in complex with peptides containing two DPF motifs. The peptides bind to a novel ligand-binding site of the ?HD, which is distinct from those of other distantly related ?HD-containing proteins. The two DPF motifs, which adopt three-dimensional structures stabilized by sequence-specific intramotif and intermotif interactions, are extensively recognized by the ?HD and are both required for binding. Thus, consecutive and singly scattered DPF motifs play distinct roles in ?HD binding.

SUBMITTER: Shimada A 

PROVIDER: S-EPMC4731787 | biostudies-literature | 2016 Jan

REPOSITORIES: biostudies-literature