Prion protein 90-231 contains a streptavidin-binding motif.
The biological function of prion protein (PrP) and the physiological relevance of its truncated subtypes and glycoforms is still enigmatic. In this paper, we adduce evidence that recombinant murine PrP fragment 90-231 (mPrP90-231) contains a biotin-mimicking sequence motif that causes binding of the bacterial protein streptavidin to mPrP90-231. As indicated by epitope mapping and proven by analysis of a deletion mutant (mPrP101-231), streptavidin binding is primarily mediated by the amino-terminus of mPrP90-231 with the core-binding sequence represented by residues 94-100. Competition with biotin significantly reduces the interaction pointing to an involvement of streptavidin's biotin-binding site (BBS). Since the BBS of streptavidin shares similarities with the active sites of proteins involved in biotin metabolism we speculate that biotin mimicry by truncated PrP-species may have an impact in vivo.
Boetel
Thurid
T
Abteilung Klinische Medizin, Forschungszentrum Borstel, Parkallee 22, D-23845 Borstel, Germany.
Bade
Steffen
S
Schmidt
Marcus Alexander
MA
Frey
Andreas
A
D020816:Amino Acid Motifs; D000818:Animals; D001665:Binding Sites; D001710:Biotin / Q000737:chemistry; D000939:Epitopes / Q000737:chemistry; D017353:Gene Deletion; D007202:Indicators and Reagents / Q000737:chemistry; D051379:Mice; D009154:Mutation; D000072002:Prion Proteins; D011328:Prions / Q000737:chemistry*; D011485:Protein Binding; D011498:Protein Precursors / Q000737:chemistry*; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000737:chemistry; D019809:Streptavidin / Q000737:chemistry*
D000939:Epitopes; D007202:Indicators and Reagents; D000072002:Prion Proteins; D011328:Prions; C512657:Prnp protein, mouse; D011498:Protein Precursors; D011994:Recombinant Proteins; D001710:Biotin; D019809:Streptavidin