NR AWIC
AU Korth,C.; Muyrers,J.; Breil,A.; Lingappa,V.R.
TI Conformational heterogeneity of the normal prion protein defined by monoclonal antibodies
QU International Conference - Prion 2006: Strategies, advances and trends towards protection of society - 3.10.-6.10.2006, Torino, Italy, Lingotto Conference Centre - Oral sessions ORAL-33
PT Konferenz-Vortrag
AB The prion protein is unique in that it can adopt several stable conformations in vivo. These conformational differences are not limited to the normal vs. the infectious conformational isoforms but have also been shown for the normal prion protein by means of in vitro translating PrP mRNA. Definite proof of conformational heterogeneity of the normal prion protein in vivo has lacked due to absence of specific ligands. Here, we present conformation-specific monoclonal antibodies (CS-mABs) specific for several conformational isoforms of the normal prion protein. These CS-mABs were raised by immunizing PrP knockout mice either with recombinant PrP produced in E. coli, or with PrP purified from brain homogenates enriched in particular conformational isoforms. One antibody, termed 19B10, recognized exclusively an unglycosylated PrP population very similar to what to NTMPrP that has been described by in vitro translation. Other CS-mABs recognized the CTM isoform. Serial immunoprecipitation experiments and distinct staining patterns of cells gave evidence for specific recognition of these mABs. Disease-dependent expression of these isoforms and the biological functions of these distinct PrP isoforms were analyzed. With these tools, we were able to prove the concept of conformational heterogeneity of the normal prion protein. Thus, different stable conformations of one polypeptide sequence can be used to differentially modify biological functions associated with the normal prion protein.
AD C. Korth, J. Muyrers, A. Breil: Institute for Neuropathology, University of Düsseldorf, Düsseldorf, Germany; V.R. Lingappa: Department Medicine and Physiology, University of California, San Francisco, USA
SP englisch
PO Italien