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Figure 2.
Figure 2: Structure of epsin ENTH bound to Ins(1,4,5)P[3]. a,
Ribbon diagrams of epsin ENTH bound to Ins(1,4,5)P[3] (Protein
DataBank (PDB) accession number 1H0A), and for comparison the
previous structures of epsin ENTH solved in the absence of
Ins(1,4,5)P[3] (PDB 1EDU14) and CALM ANTH bound to
diC[8]PtdIns(4,5)P[2] (PDB 1HFA^13). The structures are coloured
red to blue from N- to C-termini, with corresponding helices
having the same colour. Surface electrostatic potentials (red -
10 kT e^-1; blue + 10 kT e^-1) of each structure are shown
below. Ins(1,4,5)P[3] binds to CALM on a positively charged
surface not present in epsin. b, Schematic diagram of the
interactions responsible for binding the Ins(1,4,5)P[3]
molecule. c, Close-up view of the Ins(1,4,5)P[3] binding site,
showing the residues responsible for interaction with the
ligand. The hydrophobic residues L6, M10 and I13 exposed on
formation of helix 0 are also marked. The structure shows that
lipid binding and an interaction of helix 0 with the bilayer
could happen simultaneously. The electron density for the ligand
is shown, contoured at 0.168 e Å-3. d, Sequence alignments
comparing the lipid-binding residues of all the epsin family
members with corresponding residues from the ANTH domains of
AP180, CALM and LAP (the Drosophila AP180 homologue). Critical
residues for Ins(1,4,5)P[3] binding to epsin 1 are coloured in
blue and are conserved in epsins 1, 2 and 3 and in Drosophila
epsin (liquid facets). The lipid-binding residues are not well
conserved in epsinR/Drosophila epsin-like (see residues coloured
green), suggesting a different lipid specificity of this epsin.
The epsin Ins(1,4,5)P[3]-binding residues are not conserved in
AP180 and CALM, where a different set of residues have been
identified as being involved in Ins(1,4,5)P[3] binding, coloured
in purple^13. h, human; d, Drosophila; r, rat.
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