Amino acid sequence repertoire of the bacterial proteome and the occurrence of untranslatable sequences.
Bioinformatic analysis of Escherichia coli proteomes revealed that all possible amino acid triplet sequences occur at their expected frequencies, with four exceptions. Two of the four underrepresented sequences (URSs) were shown to interfere with translation in vivo and in vitro. Enlarging the URS by a single amino acid resulted in increased translational inhibition. Single-molecule methods revealed stalling of translation at the entrance of the peptide exit tunnel of the ribosome, adjacent to ribosomal nucleotides A2062 and U2585. Interaction with these same ribosomal residues is involved in regulation of translation by longer, naturally occurring protein sequences. The E. coli exit tunnel has evidently evolved to minimize interaction with the exit tunnel and maximize the sequence diversity of the proteome, although allowing some interactions for regulatory purposes. Bioinformatic analysis of the human proteome revealed no underrepresented triplet sequences, possibly reflecting an absence of regulation by interaction with the exit tunnel.
Schulich Faculty of Chemistry, Technion-Israel Institute of Technology, Technion City, Haifa 32000, Israel;
Sharon Penias
SP
Navon
Department of Structural Biology, Stanford University School of Medicine, Stanford, CA 94305-5126.
Guy
G
Kornberg
Department of Structural Biology, Stanford University School of Medicine, Stanford, CA 94305-5126.
Jin
J
Chen
Schulich Faculty of Chemistry, Technion-Israel Institute of Technology, Technion City, Haifa 32000, Israel;
Tali
T
Schwartzman
Department of Structural Biology, Stanford University School of Medicine, Stanford, CA 94305-5126.
Albert
A
Tsai
Department of Structural Biology, Stanford University School of Medicine, Stanford, CA 94305-5126.
Elisabetta Viani
EV
Puglisi
Department of Structural Biology, Stanford University School of Medicine, Stanford, CA 94305-5126 puglisi@stanford.edu nadir@tx.technion.ac.il.
Joseph D
JD
Puglisi
Schulich Faculty of Chemistry, Technion-Israel Institute of Technology, Technion City, Haifa 32000, Israel; puglisi@stanford.edu nadir@tx.technion.ac.il.
Noam
N
Adir
D003062:Codon / Q000235:genetics / Q000378:metabolism; D004926:Escherichia coli / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D029968:Escherichia coli Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D014176:Protein Biosynthesis; D020543:Proteome / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D012270:Ribosomes / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D020506:Untranslated Regions
D003062:Codon; D029968:Escherichia coli Proteins; D020543:Proteome; D020506:Untranslated Regions
bioinformatics; single-molecule methods; stalling peptides; translation; underrepresented sequences