5WTT

Structure of the 093G9 Fab in complex with the epitope peptide

Summary for 5WTT

• Entry DOI: 10.2210/pdb5wtt/pdb
• Descriptor: Heavy chain of 093G9 Fab, Light chain of 093G9 Fab, Epitope peptide of Cyr61, ... (4 entities in total)
• Functional Keywords: cyr61, epitope, rheumatoid arthritis, therapeutic antibody 093g9, protein binding
• Biological source: Homo sapiens; More
• Total number of polymer chains: 6
• Total formula weight: 107122.48

Authors

Zhong, C.,Hu, K.,Shen, J.,Ding, J. (deposition date: 2016-12-14, release date: 2017-12-20, Last modification date: 2019-01-02)

Primary citation

Zhong, C.,Huo, R.,Hu, K.,Shen, J.,Li, D.,Li, N.,Ding, J.
Molecular basis for the recognition of CCN1 by monoclonal antibody 093G9.
J. Mol. Recognit., 30:-, 2017

PubMed Abstract: CCN1, also named Cyr61 (cysteine-rich protein 61), is the first identified member of the CCN family that is composed of 6 secreted extracellular matrix-associated glycoproteins. CCN1 has been demonstrated to participate in pathogenesis of rheumatoid arthritis through various pathways. A monoclonal antibody, namely, 093G9, is effective to antagonize the effects of CCN1 and hence has potential therapeutic benefits against rheumatoid arthritis. Here, we show that the epitope recognized by 093G9 is mapped to residues 77 to 80 of CCN1, and a cyclic peptide encompassing residues 75 to 81 of CCN1 displays high binding affinity for 093G9. The crystal structure of the 093G9 Fab in complex with the cyclic peptide was determined at 2.7 Å resolution, which reveals the intensive interactions between CCN1 and 093G9. Particularly, residues Asn79 and Phe80 of CCN1 are inserted into cavities mainly formed by residues of complementarity-determining region loop L3 and framework region L2 and by residues of complementarity-determining region loops H2 and H3, respectively, which contribute most of the interactions and therefore are critical for the recognition by 093G9. Together, these findings not only identify the epitope of CCN1 for 093G9 but also reveal the molecular mechanism of recognition and binding of CCN1 by 093G9.

PubMed: 28608634
DOI: 10.1002/jmr.2645

Experimental method

X-RAY DIFFRACTION (2.7 Å)