title: Co-evolution of multipartite interactions between an extended tmRNA tag and a robust Lon protease in Mycoplasma.
abstract: Messenger RNAs that lack in-frame stop codons promote ribosome stalling and accumulation of aberrant and potentially harmful polypeptides. The SmpB-tmRNA quality control system has evolved to solve problems associated with non-stop mRNAs, by rescuing stalled ribosomes and directing the addition of a peptide tag to the C-termini of the associated proteins, marking them for proteolysis. In Escherichia coli, the ClpXP system is the major contributor to disposal of tmRNA-tagged proteins. We have shown that the AAA+ Lon protease can also degrade tmRNA-tagged proteins, but with much lower efficiency. Here, we present a unique case of enhanced recognition and degradation of an extended Mycoplasma pneumoniae (MP) tmRNA tag by the MP-Lon protease. We demonstrate that MP-Lon can efficiently and selectively degrade MP-tmRNA-tagged proteins. Most significantly, our studies reveal that the larger (27 amino acids long) MP-tmRNA tag contains multiple discrete signalling motifs for efficient recognition and rapid degradation by Lon. We propose that higher-affinity multipartite interactions between MP-Lon and the extended MP-tmRNA tag have co-evolved from pre-existing weaker interactions, as exhibited by Lon in E. coli, to better fulfil the function of MP-Lon as the sole soluble cytoplasmic protease responsible for the degradation of tmRNA-tagged proteins.
authors.affiliation: Department of Biochemistry and Cell Biology, Stony Brook University, Stony Brook, NY 11794, USA.
authors.forename: Zhiyun
authors.initials: Z
authors.lastname: Ge
authors.forename: A Wali
authors.initials: AW
authors.lastname: Karzai
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D010450:Endopeptidases / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D019143:Evolution, Molecular; D005095:Exoribonucleases / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D015964:Gene Expression Regulation, Bacterial; D008969:Molecular Sequence Data; D009174:Mycoplasma / Q000235:genetics / Q000378:metabolism*; D009690:Nucleic Acid Conformation; D049070:Protease La / Q000235:genetics / Q000378:metabolism*; D017510:Protein Folding; D012329:RNA, Bacterial / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012270:Ribosomes / Q000378:metabolism
chemical_list: D012329:RNA, Bacterial; D012333:RNA, Messenger; C096222:tmRNA; D005095:Exoribonucleases; D010450:Endopeptidases; D049070:Protease La