Crystal structure of HAb18G/CD147: implications for immunoglobulin superfamily homophilic adhesion.
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.
Yu
Xiao-Ling
XL
Cell Engineering Research Center & Department of Cell Biology, State Key Laboratory of Cancer Biology, Xijing Hospital, the Fourth Military Medical University, Xi'an, China.
Hu
Tiancen
T
Du
Jia-Mu
JM
Ding
Jian-Ping
JP
Yang
Xiang-Min
XM
Zhang
Jian
J
Yang
Bin
B
Shen
Xu
X
Zhang
Zheng
Z
Zhong
Wei-De
WD
Wen
Ning
N
Jiang
Hualiang
H
Zhu
Ping
P
Chen
Zhi-Nan
ZN
D000595:Amino Acid Sequence; D051926:Basigin / Q000737:chemistry*; D014408:Biomarkers, Tumor; D045744:Cell Line, Tumor; D018360:Crystallography, X-Ray; D019281:Dimerization; D006801:Humans; D007136:Immunoglobulins / Q000737:chemistry*; D008958:Models, Molecular; D008968:Molecular Conformation; D008969:Molecular Sequence Data; D009362:Neoplasm Metastasis; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid; D013816:Thermodynamics
C497886:BSG protein, human; D014408:Biomarkers, Tumor; D007136:Immunoglobulins; D051926:Basigin