title: Neisseria meningitidis Translation Elongation Factor P and Its Active-Site Arginine Residue Are Essential for Cell Viability.
abstract: Translation elongation factor P (EF-P), a ubiquitous protein over the entire range of bacterial species, rescues ribosomal stalling at consecutive prolines in proteins. In Escherichia coli and Salmonella enterica, the post-translational β-lysyl modification of Lys34 of EF-P is important for the EF-P activity. The β-lysyl EF-P modification pathway is conserved among only 26-28% of bacteria. Recently, it was found that the Shewanella oneidensis and Pseudomonas aeruginosa EF-P proteins, containing an Arg residue at position 32, are modified with rhamnose, which is a novel post-translational modification. In these bacteria, EF-P and its Arg modification are both dispensable for cell viability, similar to the E. coli and S. enterica EF-P proteins and their Lys34 modification. However, in the present study, we found that EF-P and Arg32 are essential for the viability of the human pathogen, Neisseria meningitidis. We therefore analyzed the modification of Arg32 in the N. meningitidis EF-P protein, and identified the same rhamnosyl modification as in the S. oneidensis and P. aeruginosa EF-P proteins. N. meningitidis also has the orthologue of the rhamnosyl modification enzyme (EarP) from S. oneidensis and P. aeruginosa. Therefore, EarP should be a promising target for antibacterial drug development specifically against N. meningitidis. The pair of genes encoding N. meningitidis EF-P and EarP suppressed the slow-growth phenotype of the EF-P-deficient mutant of E. coli, indicating that the activity of N. meningitidis rhamnosyl-EF-P for rescuing the stalled ribosomes at proline stretches is similar to that of E. coli β-lysyl-EF-P. The possible reasons for the unique requirement of rhamnosyl-EF-P for N. meningitidis cells are that more proline stretch-containing proteins are essential and/or the basal ribosomal activity to synthesize proline stretch-containing proteins in the absence of EF-P is lower in this bacterium than in others.
authors: RIKEN Structural Biology Laboratory, 1-7-22 Suehiro-cho, Tsurumi, Yokohama 230-0045, Japan.|RIKEN Systems and Structural Biology Center, 1-7-22 Suehiro-cho, Tsurumi, Yokohama 230-0045, Japan.
authors: Tatsuo
authors: T
authors: Yanagisawa
authors: National Institute of Infectious Disease, Department of Bacteriology, 1-23-1 Toyama, Shinjuku-ku, Tokyo 162-8640, Japan.
authors: Hideyuki
authors: H
authors: Takahashi
authors: RIKEN Center for Sustainable Resource Science (CSRS), 2-1 Hirosawa, Wako, Saitama 351-0198, Japan.
authors: Takehiro
authors: T
authors: Suzuki
authors: RIKEN Center for Sustainable Resource Science (CSRS), 2-1 Hirosawa, Wako, Saitama 351-0198, Japan.|National Maritime Research Institute, 6-38-1 Shinkawa, Mitaka, Tokyo 181-0004, Japan.
authors: Akiko
authors: A
authors: Masuda
authors: RIKEN Center for Sustainable Resource Science (CSRS), 2-1 Hirosawa, Wako, Saitama 351-0198, Japan.
authors: Naoshi
authors: N
authors: Dohmae
authors: RIKEN Structural Biology Laboratory, 1-7-22 Suehiro-cho, Tsurumi, Yokohama 230-0045, Japan.|RIKEN Systems and Structural Biology Center, 1-7-22 Suehiro-cho, Tsurumi, Yokohama 230-0045, Japan.
authors: Shigeyuki
authors: S
authors: Yokoyama
mesh_terms: D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001120:Arginine / Q000737:chemistry / Q000378:metabolism*; D005075:Biological Evolution; D020134:Catalytic Domain / Q000235:genetics*; D017353:Gene Deletion; D016680:Genome, Bacterial; D006031:Glycosylation; D006801:Humans; D050296:Microbial Viability / Q000235:genetics*; D008969:Molecular Sequence Data; D009345:Neisseria meningitidis / Q000187:drug effects / Q000502:physiology*; D010445:Peptide Elongation Factors / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D011392:Proline / Q000378:metabolism; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D012210:Rhamnose / Q000378:metabolism; D012270:Ribosomes / Q000378:metabolism; D053719:Tandem Mass Spectrometry
chemical_list: D000900:Anti-Bacterial Agents; D010445:Peptide Elongation Factors; C020746:factor EF-P; D001120:Arginine; D011392:Proline; D012210:Rhamnose