Antibody C219 recognizes an a-helical epitope on P-glycoprotein


van den Elsen, J. M. H., Kuntz, D. A., Hoedemaeker, F. J. and Rose, D. R., 1999. Antibody C219 recognizes an a-helical epitope on P-glycoprotein. Proceedings of the National Academy of Sciences of the United States of America (PNAS), 96 (24), pp. 13679-13684.

Related documents:

This repository does not currently have the full-text of this item.
You may be able to access a copy if URLs are provided below.

Official URL:


The ABC transporter, P-glycoprotein, is an integral membrane protein that mediates the ATP-driven efflux of drugs from multidrug-resistant cancer and HIV-infected cells. Anti-P-glycoprotein antibody C219 binds to both of the ATP-binding regions of P-glycoprotein and has been shown to inhibit its ATPase activity and drug binding capacity. C219 has been widely used in a clinical setting as a tumor marker, but recent observations of cross-reactivity with other proteins, including the c-erbB2 protein in breast cancer cells, impose potential limitations in detecting P-glycoprotein. We have determined the crystal structure at a resolution of 2.4 angstrom of the variable fragment of C219 in complex with an epitope peptide derived from the nucleotide binding domain of P-glycoprotein. The 14-residue peptide adopts an amphipathic α -helical conformation, a secondary structure not previously observed in structures of antibody-peptide complexes. Together with available biochemical data, the crystal structure of the C219-peptide complex indicates the molecular basis of the cross-reactivity of C219 with non-multidrug resistance-associated proteins. Alignment of the C219 epitope with the recent crystal structure of the ATP-binding subunit of histidine permease suggests a structural basis for the inhibition of the ATP and drug binding capacity of P-glycoprotein by C219. The results provide a rationale for the development of C219 mutants with improved specificity and affinity that could be useful in antibody-based P-glycoprotein detection and therapy in multidrug resistant cancers.


Item Type Articles
Creatorsvan den Elsen, J. M. H., Kuntz, D. A., Hoedemaeker, F. J. and Rose, D. R.
DepartmentsFaculty of Science > Biology & Biochemistry
ID Code18279


Actions (login required)

View Item