5AWT: Crystal Structure Of The Sgip1 Mu Homology Domain In Complex With An Eps15 Fragment Containing Two Dpf Motifs (ydpfggdpfkg)

FCHo1, FCHo2, and SGIP1 are key regulators of clathrin-mediated endocytosis. Their mu homology domains (muHDs) 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 muHD-binding site in Eps15 is a region encompassing six consecutive DPF motifs, while the minimal muHD-binding unit is two consecutive DPF motifs. We present the crystal structures of the SGIP1 muHD in complex with peptides containing two DPF motifs. The peptides bind to a novel ligand-binding site of the muHD, which is distinct from those of other distantly related muHD-containing proteins. The two DPF motifs, which adopt three-dimensional structures stabilized by sequence-specific intramotif and intermotif interactions, are extensively recognized by the muHD and are both required for binding. Thus, consecutive and singly scattered DPF motifs play distinct roles in muHD binding.
PDB ID: 5AWTDownload
MMDB ID: 140940
PDB Deposition Date: 2015/7/8
Updated in MMDB: 2016/08
Experimental Method:
x-ray diffraction
Resolution: 2.7  Å
Source Organism:
Similar Structures:
Biological Unit for 5AWT: dimeric; determined by author
Molecular Components in 5AWT
Label Count Molecule
Proteins (2 molecules)
Sh3-containing Grb2-like Protein 3-interacting Protein 1(Gene symbol: SGIP1)
Molecule annotation
Epidermal Growth Factor Receptor Substrate 15
Molecule annotation
Chemicals (6 molecules)
* Click molecule labels to explore molecular sequence information.

Citing MMDB