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Figure 3.
Crystal structure of the PCSK9ΔC-EGF(AB) complex. Ribbon (A)
and surface (B) representations, in the same orientation, of the
complex formed between PCSK9ΔC and EGF(A) (yellow). EGF(A)
contacts PCSK9 via the catalytic domain (red) but not the
prodomain (blue). The P′ helix, which is part of the catalytic
domain, is shown in pink. Dotted lines represent PCSK9 residues
for which no electron density was observed. C, transparent
surface representation of PCSK9ΔC; blue-labeled patches
indicate residues contacted by EGF(A) (yellow ribbon; the yellow
sphere is the Ca^2+ ion). Contacts are all less than 4 Å.
Asp-374 (PCSK9) is at the tip of a β-hairpin loop. EGF(A)
His-306 adopts a conformation that does not allow interaction
with Asp-374 at neutral pH. Ser-153 is the N terminus of the
PCSK9 catalytic domain generated upon autocleavage. Hydrogen
bonds are established between side chain atoms of the following
pairs of residues from PCSK9 and EGF(A): Arg-194 to Asp-310 and
Asn-295, Asp-238 to Asn-295, Thr-377 to Asn-309 and Asp-310, and
between backbone atoms for Thr-377 to Asp-310 and Phe-379 to
Cys-308. D, transparent surface representation of EGF(A);
yellow-labeled patches indicate residues contacted by PCSK9ΔC.
The protein is oriented as if removing PCSK9ΔC from the complex
shown in panel C followed by a 180° y axis rotation.
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