New insight into the species barrier of mammalian prions obtained from structure-based conservation analysis.

OBJECTIVES

The structures of several mammalian prions have been determined by NMR; however, their transmission and evolutionary features are still unclear. The objective of this study is to explore species barrier information from their structures.

METHODS

In this study, we compared the functional domains (121-231) of 8 mammalian prions with structure-based conservation analysis using visual molecular dynamic software (version 1.8.5).

RESULTS

Residues 184, 203 and 205, which play important roles in modulating the transmission of prion diseases, were identified as a structure-conserved domain rather than sequence-conserved domain of mammalian prions. The phylogenetic tree was reconstructed based on structure conservation. The topology of the tree explains the species barrier during the transmission of mammalian prions which cannot be deduced by the sequence phylogenetic tree.

CONCLUSIONS

These results suggest that structure-based analysis is more accurate and informative than sequence-based analysis in the study of prion transmission and evolution.