Elongation factor P explained

Symbol:EFP_N
Elongation factor P (EF-P) KOW-like domain
Pfam:PF08207
Pfam Clan:CL0107
Interpro:IPR013185
Prosite:PDOC00981
Symbol:EFP
Elongation factor P (EF-P) OB domain
Pfam:PF01132
Pfam Clan:CL0021
Interpro:IPR001059
Prosite:PDOC00981
Cdd:cd04470
Symbol:Elong-fact-P_C
Elongation factor P, C-terminal
Pfam:PF09285
Interpro:IPR015365
Scop:1ueb
Cdd:cd05794

EF-P (elongation factor P) is an essential protein that in bacteria stimulates the formation of the first peptide bonds in protein synthesis.[1] [2] Studies show that EF-P prevents ribosomes from stalling during the synthesis of proteins containing consecutive prolines. EF-P binds to a site located between the binding site for the peptidyl tRNA (P site) and the exiting tRNA (E site). It spans both ribosomal subunits with its amino-terminal domain positioned adjacent to the aminoacyl acceptor stem and its carboxyl-terminal domain positioned next to the anticodon stem-loop of the P site-bound initiator tRNA.[3] The EF-P protein shape and size is very similar to a tRNA and interacts with the ribosome via the exit “E” site on the 30S subunit and the peptidyl-transferase center (PTC) of the 50S subunit.[4] EF-P is a translation aspect of an unknown function, therefore It probably functions indirectly by altering the affinity of the ribosome for aminoacyl-tRNA, thus increasing their reactivity as acceptors for peptidyl transferase.

EF-P consists of three domains:

Eukaryotes and archaea lack EF-P. In these domains, a similar function is performed by the archaeo-eukaryotic initiation factor, a/eIF-5A, which exhibits some modest sequence and structural similarity with EF-P.[6] There are, however, important differences between EF-p and eIF-5A. (a) EF-P has a structure similar to that of L-shaped tRNA and it contains three (I,II and III) β-barrel domains. In contrast, eIF-5A contains only two domains (C and N) with a corresponding size difference. (b) Moreover, as opposed to eIF-5A, which contains the non-proteinogenic amino acid hypusine that is essential for its activity, EF-P displays a diversity of post-transcriptional modifications at the analogous position (β-lysylation of lysine residue, rhamnosylation of arginine residue, or none at all).[7] [8]

Function

In eubacteria, there are three groups of factors that promote protein synthesis: initiation factors, elongation factors and termination factors. The elongation phase of translation is promoted by three universal elongation factors, EF-Tu, EF-Ts, and EF-G.[9] EF-P was discovered in 1975 by Glick and Ganoza,[10] as a factor that increased the yield of peptide bond formation between initiator fMet-tRNA(fMet) and a mimic of aa-tRNA, puromycin (Pmn). The low yield of product formation in absence of EF-P can be described by the loss of peptidyl-tRNA from the stalled ribosome. Thus, EF-P is not a necessary component of minimal in vitro translation system, however, the absence of EF-P can limit translation rate, increase antibiotic sensitivity, and slow growth.

To complete its function, EF-P enters paused ribosomes through the E-site and facilitates peptide bond formation through interactions with the P-site tRNA.[11] EF-P and eIF-5A both are essential for the synthesis of a subset of proteins containing proline stretches in all cells.

It has been suggested that after binding of the initiator tRNA to the P/I site, it is correctly positioned to the P site by binding of EF-P to the E site.[12] Additionally, EF-P has been shown to assist in efficient translation of three or more consecutive proline residues.[13]

Structure

EF-P is a 21 kDa protein encoded by the efp gene. EF-P consists of three β-barrel domains (I,II and III) and has a L shape tRNA structure. Domain II and III of EF-P are similar to each other. Despite the structural similarity of EF-P with tRNA, studies showed that EF-P does not bind to the ribosome at the classical tRNA binding site, but at the distinct position that is located between the P and E sites.

See also

Notes and References

  1. Doerfel LK, Wohlgemuth I, Kothe C, Peske F, Urlaub H, Rodnina MV . EF-P is essential for rapid synthesis of proteins containing consecutive proline residues . Science . 339 . 6115 . 85–8 . January 2013 . 23239624 . 10.1126/science.1229017 . 20153355 . 2013Sci...339...85D . 11858/00-001M-0000-0010-8D55-5 . free .
  2. Hanawa-Suetsugu K, Sekine S, Sakai H, Hori-Takemoto C, Terada T, Unzai S, Tame JR, Kuramitsu S, Shirouzu M, Yokoyama S . 6 . Crystal structure of elongation factor P from Thermus thermophilus HB8 . Proceedings of the National Academy of Sciences of the United States of America . 101 . 26 . 9595–600 . June 2004 . 15210970 . 470720 . 10.1073/pnas.0308667101 . 2004PNAS..101.9595H . free .
  3. Blaha G, Stanley RE, Steitz TA . Formation of the first peptide bond: the structure of EF-P bound to the 70S ribosome . Science . 325 . 5943 . 966–70 . August 2009 . 19696344 . 3296453 . 10.1126/science.1175800 . 2009Sci...325..966B .
  4. Elgamal S, Katz A, Hersch SJ, Newsom D, White P, Navarre WW, Ibba M . EF-P dependent pauses integrate proximal and distal signals during translation . PLOS Genetics . 10 . 8 . e1004553 . August 2014 . 25144653 . 4140641 . 10.1371/journal.pgen.1004553 . free .
  5. Hanawa-Suetsugu K, Sekine S, Sakai H, Hori-Takemoto C, Terada T, Unzai S, Tame JR, Kuramitsu S, Shirouzu M, Yokoyama S . 6 . Crystal structure of elongation factor P from Thermus thermophilus HB8 . Proceedings of the National Academy of Sciences of the United States of America . 101 . 26 . 9595–600 . June 2004 . 15210970 . 470720 . 10.1073/pnas.0308667101 . 2004PNAS..101.9595H . free .
  6. Rossi D, Kuroshu R, Zanelli CF, Valentini SR . eIF5A and EF-P: two unique translation factors are now traveling the same road . Wiley Interdisciplinary Reviews. RNA . 5 . 2 . 209–22 . 2013 . 24402910 . 10.1002/wrna.1211 . 25447826 .
  7. Park JH, Johansson HE, Aoki H, Huang BX, Kim HY, Ganoza MC, Park MH . Post-translational modification by β-lysylation is required for activity of Escherichia coli elongation factor P (EF-P) . The Journal of Biological Chemistry . 287 . 4 . 2579–90 . January 2012 . 22128152 . 3268417 . 10.1074/jbc.M111.309633 . free .
  8. Volkwein . Wolfram . Krafczyk . Ralph . Jagtap . Pravin Kumar Ankush . Parr . Marina . Mankina . Elena . Macošek . Jakub . Guo . Zhenghuan . Fürst . Maximilian Josef Ludwig Johannes . Pfab . Miriam . Frishman . Dmitrij . Hennig . Janosch . Jung . Kirsten . Lassak . Jürgen . Switching the Post-translational Modification of Translation Elongation Factor EF-P . Frontiers in Microbiology . 24 May 2019 . 10 . 1148 . 10.3389/fmicb.2019.01148. 31178848 . 6544042 . free .
  9. Doerfel LK, Rodnina MV . Elongation factor P: Function and effects on bacterial fitness . Biopolymers . 99 . 11 . 837–45 . November 2013 . 23828669 . 10.1002/bip.22341 . free . 11858/00-001M-0000-0013-F8DD-5 .
  10. Glick BR, Ganoza MC . Identification of a soluble protein that stimulates peptide bond synthesis . Proceedings of the National Academy of Sciences of the United States of America . 72 . 11 . 4257–60 . November 1975 . 1105576 . 10.1073/pnas.72.11.4257 . 388699 . 1975PNAS...72.4257G . free .
  11. Tollerson R, Witzky A, Ibba M . Elongation factor P is required to maintain proteome homeostasis at high growth rate . Proceedings of the National Academy of Sciences of the United States of America . 115 . 43 . 11072–11077 . October 2018 . 30297417 . 6205485 . 10.1073/pnas.1812025115 . 2018PNAS..11511072T . free .
  12. Liljas A . Leaps in translational elongation. . Science . October 2009 . 326 . 5953 . 677–8 . 10.1126/science.1181511 . 19833922 . 45692923 .
  13. Ude S, Lassak J, Starosta AL, Kraxenberger T, Wilson DN, Jung K . Translation elongation factor EF-P alleviates ribosome stalling at polyproline stretches . Science . 339 . 6115 . 82–5 . January 2013 . 23239623 . 10.1126/science.1228985 . 206544633 . 2013Sci...339...82U . free .

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