Crystal Structure of HAb18G/CD147: IMPLICATIONS FOR IMMUNOGLOBULIN SUPERFAMILY HOMOPHILIC ADHESION

• Published in: The Journal of biological chemistry Vol. 283; no. 26; pp. 18056 - 18065
• Main Authors: Yu, Xiao-Ling, Hu, Tiancen, Du, Jia-Mu, Ding, Jian-Ping, Yang, Xiang-Min, Zhang, Jian, Yang, Bin, Shen, Xu, Zhang, Zheng, Zhong, Wei-De, Wen, Ning, Jiang, Hualiang, Zhu, Ping, Chen, Zhi-Nan
• Format: Journal Article
• Language: English
• Published: United States American Society for Biochemistry and Molecular Biology 27.06.2008
• Subjects: Amino Acid Sequence; Basigin - chemistry; Biomarkers, Tumor; Cell Line, Tumor; Crystallography, X-Ray; Dimerization; Humans; Immunoglobulins - chemistry; Models, Molecular; Molecular Conformation; Molecular Sequence Data; Neoplasm Metastasis; Protein Structure, Tertiary; Sequence Homology, Amino Acid; Thermodynamics
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M802694200

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 2.8Å 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.