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Structural basis for the recognition of two consecutive mutually interacting DPF motifs by the SGIP1 μ homology

Atsushi Shimada1,2, Atsuko Yamaguchi1, Daisuke Kohda1

  • 1Division of Structural Biology, Medical Institute of Bioregulation, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.

Scientific Reports
|January 30, 2016
PubMed

Insights

Key regulators of clathrin-mediated endocytosis, FCHo1, FCHo2, and SGIP1, bind Eps15 via Asp-Pro-Phe (DPF) motifs. Two consecutive DPF motifs form the minimal binding unit, interacting with a novel SGIP1 μHD site.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Structural Biology

Background:

  • Clathrin-mediated endocytosis is crucial for cellular processes.
  • FCHo1, FCHo2, and SGIP1 are regulators of endocytosis, interacting with Eps15.
  • Eps15 contains numerous Asp-Pro-Phe (DPF) motifs that bind to μ homology domains (μHDs).

Purpose of the Study:

  • To determine the minimal binding unit of Eps15 for μHD interaction.
  • To elucidate the structural basis of the interaction between SGIP1 μHD and DPF motifs.
  • To characterize the binding site and the role of consecutive DPF motifs.

Main Methods:

  • X-ray crystallography to determine the structure of SGIP1 μHD with DPF peptides.
  • Peptide-based binding assays.
  • Bioinformatic analysis of μHD-containing proteins.

Main Results:

  • The high-affinity binding site in Eps15 comprises six consecutive DPF motifs.
  • The minimal binding unit is two consecutive DPF motifs.
  • Crystal structures reveal a novel ligand-binding site on SGIP1 μHD for two DPF motifs.
  • DPF motifs adopt specific 3D structures stabilized by intra- and inter-motif interactions.
  • Both DPF motifs are essential for μHD binding.

Conclusions:

  • Consecutive DPF motifs play a distinct and crucial role in μHD binding compared to scattered motifs.
  • The identified binding mode is unique to SGIP1 μHD among related proteins.
  • This study provides detailed insights into the molecular recognition mechanism of endocytic scaffold proteins.

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