2fat
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An anti-urokinase plasminogen activator receptor (UPAR) antibody: Crystal structure and binding epitope
OverviewOverview
Human urokinase-type plasminogen activator receptor (uPAR/CD87) is, expressed at the invasive interface of the tumor-stromal microenvironment, in many human cancers and interacts with a wide array of extracellular, molecules. An anti-uPAR antibody (ATN615) was prepared using hybridoma, technology. This antibody binds to uPAR in vitro with high affinity (K(d), approximately 1 nM) and does not interfere with uPA binding to uPAR. Here, we report the crystal structure of the Fab fragment of ATN615 at 1.77 A, and the analysis of ATN615-suPAR-ATF structure that was previously, determined, emphasizing the ATN615-suPAR interaction. The complementarity, determining regions (CDRs) of ATN615 consist of a high percentage of, aromatic residues, and form a relatively flat and undulating surface. The, ATN615 Fab fragment recognizes domain 3 of suPAR. The antibody-antigen, recognition involves 11 suPAR residues and 12 Fab residues from five CDRs., Structural data suggest that Pro188, Asn190, Gly191, and Arg192 residues, of uPAR are the key residues for the antibody recognition, while Pro189, and Arg192 render specificity of ATN615 for human uPAR. Interestingly, this antibody-antigen interface has a small contact area, mainly polar, interaction with little hydrophobic character, yet has high binding, strength. Furthermore, several solvent molecules (assigned as polyethylene, glycols) were clearly visible in the binding interface between antibody, and antigen, suggesting that solvent molecules may be important for the, maximal binding between suPAR and ATN615 Fab. ATN615 undergoes small but, noticeable changes in its CDR region upon antigen binding.
About this StructureAbout this Structure
2FAT is a Single protein structure of sequence from Mus musculus. Full crystallographic information is available from OCA.
ReferenceReference
An anti-urokinase plasminogen activator receptor (uPAR) antibody: crystal structure and binding epitope., Li Y, Parry G, Chen L, Callahan JA, Shaw DE, Meehan EJ, Mazar AP, Huang M, J Mol Biol. 2007 Jan 26;365(4):1117-29. Epub 2006 Oct 21. PMID:17101149
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