Molecular cloning of the cDNA coding for Xenopus laevis prion protein

Abstract

Isolation and characterization of the cDNA coding for the 216-residue Xenopus laevis prion protein is reported. Existence of this protein in amphibians was suggested by an EST fragment (accession number BG813008), while a conclusive demonstration is presented here. This protein exhibits a higher identity level to avian and turtle prion (more than 44%) than to mammalian prion (about 28%). Although most of the structural motifs common to known prion proteins are conserved in X. laevis, the lack of repeats represents a substantial difference. Other features worth noting are the presence of not perfectly conserved hydrophobic stretch, which is considered the prion signature, as well as the complete absence of histidine residues. ß

Disruption of Doppel prevents neurodegeneration in mice with extensive Prnp deletions

“…The Prnp gene is conserved in mammals (27), and paralogues are present in turtle (28), fish (29,30), and amphibians (31), suggesting an important function of PrP C . No natural Prnp null alleles were described despite negative evolutionary pressure (32).…”

New insights into cellular prion protein (PrPc) functions: The “ying and yang” of a relevant protein

“…However, alignments of human and mammalian PRNP sequences indicate that codons located between residues 90 and 130 influence the transmissibility of prions in mammals, including humans (Schatzl et al, 1995). In addition, some paralogue genes have been described in chicken, amphibians, reptiles and fish (Gabriel et al, 1992;Simonic et al, 2000;Strumbo et al, 2001;Suzuki et al, 2002) 2. Tissue and cellular expression of PrP c : from the whole organism to the neuronal synapse.…”

Prion protein NMR structures of chickens, turtles, and frogs

“…Healthy organisms that do not express a prion protein, such as suitably selected transgenic laboratory animals, cannot develop a TSE (2), and the ''protein-only hypothesis'' further attributes TSE-causing infectivity to an aggregated ''scrapie form'' of PrP (PrP SC ) that has been isolated from brain tissue of diseased organisms (1). Although TSEs have only been documented for mammalian species, PrP has been identified in a wider range of higher organisms, which on an evolutionary scale extends at least down to amphibians (3)(4)(5)(6)(7)(8)(9). In apparent contrast to the high sequence conservation among mammalian PrPs, no physiological function has been reliably attributed to the ''cellular form'' of PrP (PrP C ) found in healthy organisms.…”