Structural and functional study of translational release factor from the viewpoint of molecular mimicry and prion transmission

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Recent molecular and structural studies including those from this laboratory have revealed that proteins called translation factors mimic the shape of tRNA. One of them, a polypeptide release factor, encodes a tripeptide that serves as an ‘anticodon' to decipher stop codons in mRNA. These findings let us to propose the novel concept of macromolecular mimicry between protein and RNA. Moreover, The [PSI^+] element of budding yeast represents the prion conformation of translation release factor eRF3 that is propagated and transmitted in the cytoplasm. On many levels, yeast prions are analogous to mammalian prions and much interest lies in understanding how prions are able to generate variation in isogenic strains. We have investigated translational release factors from the viewpoint of molecular mimicry and prion transmission, and uncovered the following aspects.1)Omnipotent decoding potential resides in eRF1 of variant-code organisms and is modulated by the interactions of amino acid seq … More uences within the domain 1.2)Polypeptide release at sense and noncognate stop codons by localized charge-exchange alterations in translational release factors.3)EF-G participates in ribosome disassembly by interacting with ribosome recycling factor RRF at their tRNA-mimicry domains.4)Yeast [PSI^+] prions that are crosstransmissible and susceptible beyond a species barrier through a quasi-prion state.5)The critical role of the universally conserved A2602 of 23S rRNA in the release of the nascent peptide during translation termination.6)Crystal structure and functional analysis of the eukaryotic class II release factor eRF3 from S.Pombe.7)Part of the prion domain of yeast eRF3 masks the eRF3-binding site in eRF1.8)RRF disassembles the posttermination ribosomal complex independent of the ribosomal translocase activity of EF-G.9)Heterologous expression of A.aeolicus RRF in E.coli is dominant lethal by forming a complex that lacks functional coordination for ribosome disassembly.10)Conformational memory preserved in a weak-to-strong or strong-to-weak [PSI^+] conversion during transmission to Sup35 prion variants. Less