Prions are self-perpetuating aggregated proteins, associated with human and animal diseases, and controlling yeast heritable traits. Cross-species prion transmission is impaired by differences between protein sequences involved in intermolecular interactions. However, this barrier could be overcome, e. g. in case of ‘mad cow’ disease transmission to humans. We are studying cross-species interactions between derivatives of the yeast prion protein Sup35 from different yeast species. Transmission of prion state occurs between the Sup35 proteins of very distant species, Ogateae methanolica and Saccharomyces cerevisiae, with only 40% of amino acid similarity in their prion domains, although it is not detected between Sup35 proteins of more closely related species. This shows that transmission barriers do not always correlate with the sequence identity. We present data on the sequence features and aggregation properties of O. methanolica prion domain that may explain this phenomenon. Comprehensive studies of the parameters of protein aggregates formed by Sup35 prion domains of different origins and structures in the S. cerevisiae cells are also performed.