The EH1 Domain of Eps15 Is Structurally Classified as a
Member of the S100 Subclass of EF-Hand-Containing
Proteins
The Eps15 homology (EH) domain is a protein-protein
interaction module that binds to proteins containing the
asparagine-proline-phenylalanine (NPF) or
tryptophan/phenylalanine-tryptophan (W/FW) motif. EH
domain-containing proteins serve important roles in
signaling and processes connected to transport, protein
sorting, and organization of subcellular structure. Here,
we report the solution structure of the apo form of the EH1
domain of mouse Eps15, as determined by high-resolution
multidimensional heteronuclear NMR spectroscopy. The
polypeptide folds into six R-helices and a short
antiparallel ‚-sheet. Additionally, it contains a
long, structured, topologically unique C-terminal loop.
Helices 2-5 form two EF-hand motifs. Structural similarity
and Ca2+ binding properties lead to classification of the
EH1 domain as a member of the S100 subclass of
EF-hand-containing proteins, albeit with a unique set of
interhelical angles. Binding studies using an eight-residue
NPF-containing peptide derived from RAB, the cellular
cofactor of the HIV Rev protein, show a hydrophobic
peptide-binding pocket formed by conserved tryptophan and
leucine residues.
PDB code 1QJT. (
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■ Whitehead, B., Tessari, M., Versteeg, H.H., van
Delft, S., van Bergen en Henegouwen, P.M.P., & Vuister,
G.W. (1998) “Sequence-specific 1H, 13C and 15N
assignment of the EH1 domain of mouse Eps15”,
J.
Biomol. NMR 12, 465-466.
■ Whitehead, B., Tessari, M., Carotenuto, A., Bergen
en Henegouwen, P.M.P. van, & Vuister, G.W. (1999)
“The EH1 domain of Eps15 is structurally classified
as a member of the S100 subclass of EF-hand-containing
proteins,
Biochemistry 38,
11271-11277.
