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PDBsum entry 3b5h
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Cell invasion
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PDB id
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3b5h
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References listed in PDB file
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Key reference
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Title
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Crystal structure of hab18g/cd147: implications for immunoglobulin superfamily homophilic adhesion.
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Authors
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X.L.Yu,
T.Hu,
J.M.Du,
J.P.Ding,
X.M.Yang,
J.Zhang,
B.Yang,
X.Shen,
Z.Zhang,
W.D.Zhong,
N.Wen,
H.Jiang,
P.Zhu,
Z.N.Chen.
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Ref.
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J Biol Chem, 2008,
283,
18056-18065.
[DOI no: ]
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PubMed id
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Abstract
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CD147, a member of the immunoglobulin superfamily (IgSF), plays fundamental
roles in intercellular interactions in numerous pathological and physiological
processes. Importantly, our previous studies have demonstrated that HAb18G/CD147
is a novel hepatocellular carcinoma (HCC)-associated antigen, and HAb18G/CD147
stimulates adjacent fibroblasts and HCC cells to produce elevated levels of
several matrix metalloproteinases, facilitating invasion and metastasis of HCC
cells. In addition, HAb18G/CD147 has also been shown to be a novel universal
cancer biomarker for diagnosis and prognostic assessment of a wide range of
cancers. However, the structural basis underlying the multifunctional character
of CD147 remains unresolved. We report here the crystal structure of the
extracellular portion of HAb18G/CD147 at 2.8A resolution. The structure
comprises an N-terminal IgC2 domain and a C-terminal IgI domain, which are
connected by a 5-residue flexible linker. This unique C2-I domain organization
is distinct from those of other IgSF members. Four homophilic dimers exist in
the crystal and adopt C2-C2 and C2-I dimerization rather than V-V dimerization
commonly found in other IgSF members. This type of homophilic association thus
presents a novel model for homophilic interaction between C2 domains of IgSF
members. Moreover, the crystal structure of HAb18G/CD147 provides a good
structural explanation for the established multifunction of CD147 mediated by
homo/hetero-oligomerizations and should represent a general architecture of
other CD147 family members.
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Figure 3.
FIGURE 3. The sequence alignment among CD147, neuroplastin,
and embigin from various species. Bars and helices symbolize
secondary structures. The conserved residues mentioned in the
text are shaded and numbered. The disulfide bonds and
N-glycosylation sites are also denoted.
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Figure 4.
FIGURE 4. Structural superposition of HAb18G/CD147 domain 2
with the heavy-chain variable domain of Fab New and domain 1. A,
C[  ]superposition of
HAb18G/CD147 domain 2 with the VH domain of Fab New. B, C[ ]superposition of
HAb18G/CD147 domain 2 with domain 1. Molecules are depicted as
ribbons with strands labeled according to convention. The
parenthesized letters represent strands from Fab (A) or domain 2
(B). The C-C' β-bulge of domain 2 is similar to that of Fab VH
domain but absent in domain 1.
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The above figures are
reprinted
by permission from the ASBMB:
J Biol Chem
(2008,
283,
18056-18065)
copyright 2008.
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