Analysis of 27 mammalian and 9 avian PrPs reveals high conservation of flexible regions of the prion protein.
Prion diseases are fatal neurodegenerative disorders in man and animal associated with conformational conversion of a cellular prion protein (PrPc) into the pathologic isoform (PrPSc). The function of PrPcand the tertiary structure of PrPScare unclear. Various data indicate which parts of PrP might control the species barrier in prion diseases and the binding of putative factors to PrP. To elucidate these features, we analyzed the evolutionary conservation of the prion protein. Here, we add the primary PrP structures of 20 ungulates, three rodents, three carnivores, one maritime mammal, and nine birds. Within mammals and birds we found a high level of amino acid sequence identity, whereas between birds and mammals the overall homology was low. Various structural elements were conserved between mammals and birds. Using the CONRAD space-scale alignment, which predicts conserved and variable blocks, we observed similar patterns in avian and mammalian PrPs, although 130 million years of separate evolution lie in between. Our data support the suggestion that the repeat elements might have expanded differently within the various classes of vertebrates. Of note is the N-terminal part of PrP (amino acid residues 23-90), which harbors insertions and deletions, whereas in the C-terminal portion (91-231) mainly point mutations are found. Strikingly, we found a high level of conservation of sequences that are not part of the structured segment 121-231 of PrPcand of the structural elements therein, e.g. the N-terminal region from amino acid residue 23-90 and the regions located upstream of alpha-helices 1 and 3.
Wopfner
F
F
Genecenter, Department of Virology, Max von Pettenkofer-Institute for Medical Microbiology, Ludwig-Maximilians-University of Munich, Feodor-Lynen-Str. 25, Munich, 81377, Germany.
Weidenhöfer
G
G
Schneider
R
R
von Brunn
A
A
Gilch
S
S
Schwarz
T F
TF
Werner
T
T
Schätzl
H M
HM
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001717:Birds; D002415:Cats; D017124:Conserved Sequence; D018076:DNA, Complementary; D004285:Dogs; D014644:Genetic Variation; D006801:Humans; D008322:Mammals; D008969:Molecular Sequence Data; D011328:Prions / Q000145:classification / Q000235:genetics*; D012377:Rodentia; D017386:Sequence Homology, Amino Acid
D018076:DNA, Complementary; D011328:Prions