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Figure 6.
Figure 6. Structural Mimicry of Chemokine Dimer Formation
and GPCR Receptor Binding(A) Tube and surface representations of
the M3 sequestration of MCP-1(P8A). M3 NTD and CTD loops are
depicted in cyan, and the chemokine in magenta. Cys residues are
in yellow. Directly below is the same view depicting the MCP-1
(P8A) surface engaged by M3, with the intensity of the magenta
surface increased for shorter contact distances between 2.5 and
4 Å. The acidic NTD s2b-s3 loop, which engages the N-loop
region, and the CTD A-B loop, which forms an anti-parallel β
interaction with the N-terminal segment of MCP-1, are shown as
cyan tubes with their side chains displayed.(B) CC-chemokine
homodimerization as observed for MCP-1 (1DOK). Displayed is the
homodimer of MCP-1 with the magenta monomer oriented as
MCP-1(P8A) in (A). The dimer is formed dominantly by the
anti-parallel β interaction between N-terminal regions. Below
is the contact surface, highlighting the role of MCP-1 Pro8,
which is situated above the chemokine invariant Cys12-Cys52
disulfide bond in precisely the same location as M3 ProP272 in
the M3/MCP-1(P8A) complex.(C) Displayed is the NMR structure of
dimeric IL-8 in complex with a modified peptide from the N
terminus of the IL-8 receptor CXCR-1 (1ILQ). The CXC dimer is
displayed in magenta and blue and is formed through the extended
sheet formed between monomer β1-strands. The CXCR-1 receptor
fragment also binds to the N-terminal chemokine region in an
anti-parallel fashion, with Pro29 similarly packed on top of the
Cys12-Cys52 disulfide bond. Further, this receptor fragment also
engages the N-loop region with a highly acidic cluster of
residues, very similar in location to where the M3 NTD s2b-s3
loop engages MCP-1(P8A).
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