Mistletoe lectin binds to multidrug resistance-associated protein MRP5.
BACKGROUND
Mistletoe lectins (MLs) are the active components of aqueous mistletoe extracts widely used in complementary cancer therapy, however, it is not clear if they bind to carbohydrate residues only or whether they interact with proteins as well. Protein-protein interactions do not seem unlikely as MLs act at very low molar concentrations usually observed with peptide-peptide interactions only and not seen with lectin-sugar interactions.


METHODS
In order to detect protein-protein interactions a random peptide library was screened for the ability to bind to MLs.


RESULTS
MLs bound to peptides showing homologies to multidrug resistance-associated protein 5 (MRP5). However, the MLs only slightly modified the MRP5 efflux pump, while periodate treatment to inhibit cell membrane binding via glycan completely abolished the ML-I binding sites in MRP5 overexpressing cells.


CONCLUSIONS
The protein sequence is not important for ML-I binding, indicating that the biological activity of MLs can most likely be attributed to the sugar chains.
Nehmann
Nina
N
Department of Anatomy II: Experimental Morphology, University Hospital Hamburg-Eppendorf, Martinistrasse 52, D-20246 Hamburg, Germany. nnehmann@uke.unihamburg.de
Schade
Ulrika M
UM
Pfüller
Uwe
U
Schachner
Melitta
M
Schumacher
Udo
U
D002462:Cell Membrane / Q000378:metabolism*; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006801:Humans; D007124:Immunoenzyme Techniques; D007668:Kidney / Q000166:cytology / Q000378:metabolism; D037102:Lectins / Q000378:metabolism*; D014784:Mistletoe / Q000378:metabolism*; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics / Q000378:metabolism*; D019151:Peptide Library; D010504:Periodic Acid / Q000494:pharmacology; D011134:Polysaccharides / Q000378:metabolism*; D011485:Protein Binding
D037102:Lectins; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D019151:Peptide Library; D010504:Periodic Acid; D011134:Polysaccharides; C120809:ABCC5 protein, human; C009288:metaperiodate