 |
PDBsum entry 2ffk
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Virus/viral protein/cytokine
|
PDB id
|
|
|
|
2ffk
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
References listed in PDB file
|
|
|
Key reference
|
|
|
Title
|
|
Solution structure of the complex between poxvirus-Encoded cc chemokine inhibitor vcci and human mip-1beta.
|
|
|
Authors
|
|
L.Zhang,
M.Derider,
M.A.Mccornack,
S.C.Jao,
N.Isern,
T.Ness,
R.Moyer,
P.J.Liwang.
|
|
|
Ref.
|
|
Proc Natl Acad Sci U S A, 2006,
103,
13985-13990.
[DOI no: ]
|
|
|
PubMed id
|
|
|
|
|
|
|
|
|
Abstract
|
|
|
Chemokines (chemotactic cytokines) comprise a large family of proteins that
recruit and activate leukocytes, giving chemokines a major role in both immune
response and inflammation-related diseases. The poxvirus-encoded viral CC
chemokine inhibitor (vCCI) binds to many CC chemokines with high affinity,
acting as a potent inhibitor of chemokine action. We have used heteronuclear
multidimensional NMR to determine the structure of an orthopoxvirus vCCI in
complex with a human CC chemokine, MIP-1beta (macrophage inflammatory protein
1beta). vCCI binds to the chemokine with 1:1 stoichiometry, forming a complex of
311 aa. vCCI uses residues from its beta-sheet II to interact with a surface of
MIP-1beta that includes residues adjacent to its N terminus, as well as residues
in the 20's region and the 40's loop. This structure reveals the strategy used
by vCCI to tightly bind numerous chemokines while retaining selectivity for the
CC chemokine subfamily.
|
|
|
|
|
|
|
|
Figure 3.
Fig. 3. Solution structure of the vCCI:MIP-1  complex.
Superposition of 15 NMR structures is shown, with the vCCI
backbone colored red and selected side chains colored pink. The
MIP-1 backbone is blue, and
selected side chains are shown in green.
|
|
Figure 4.
Fig. 4. Detailed views of the VCCI:MIP–1 interaction. (A) MIP-1
Phe-13 (green) and the
surrounding hydrophobic residues (yellow) from vCCI. (B) View of
the 20's region and the 40's loop of MIP-1 (green) in proximity to
vCCI acidic residues (red). In the present structure, MIP-1 residues
45, 46, and 48 are changed to Ala to enhance solubility.
|
|
|
|
|
|
|
|
|
|
