Elongation factor P (EF-P) KOW-like domain
crystal structure of translation initiation factor 5a from pyrococcus horikoshii
Identifiers
SymbolEFP_N
PfamPF08207
Pfam clanCL0107
InterProIPR013185
PROSITEPDOC00981
Available protein structures:
Pfam  structures / ECOD  
PDBRCSB PDB; PDBe; PDBj
PDBsumstructure summary
Elongation factor P (EF-P) OB domain
crystal structure of translation elongation factor p from thermus thermophilus hb8
Identifiers
SymbolEFP
PfamPF01132
Pfam clanCL0021
InterProIPR001059
PROSITEPDOC00981
CDDcd04470
Available protein structures:
Pfam  structures / ECOD  
PDBRCSB PDB; PDBe; PDBj
PDBsumstructure summary
Elongation factor P, C-terminal
crystal structure of translation elongation factor p from thermus thermophilus hb8
Identifiers
SymbolElong-fact-P_C
PfamPF09285
InterProIPR015365
SCOP21ueb / SCOPe / SUPFAM
CDDcd05794
Available protein structures:
Pfam  structures / ECOD  
PDBRCSB PDB; PDBe; PDBj
PDBsumstructure summary

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.[1] 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,[1] 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:

  • An N-terminal KOW-like domain
  • A central OB domain, which forms an oligonucleotide-binding fold. It is not clear if this region is involved in binding nucleic acids[5]
  • A C-terminal domain which adopts an OB-fold, with five beta-strands forming a beta-barrel in a Greek-key topology[5]

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.[2][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.[2] (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.[7] 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 of 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.[1]

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.[9] 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.[3]

See also

References

  1. 1 2 3 4 Doerfel LK, Wohlgemuth I, Kothe C, Peske F, Urlaub H, Rodnina MV (January 2013). "EF-P is essential for rapid synthesis of proteins containing consecutive proline residues". Science. 339 (6115): 85–8. Bibcode:2013Sci...339...85D. doi:10.1126/science.1229017. hdl:11858/00-001M-0000-0010-8D55-5. PMID 23239624. S2CID 20153355.
  2. 1 2 3 Hanawa-Suetsugu K, Sekine S, Sakai H, Hori-Takemoto C, Terada T, Unzai S, et al. (June 2004). "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. Bibcode:2004PNAS..101.9595H. doi:10.1073/pnas.0308667101. PMC 470720. PMID 15210970.
  3. 1 2 Blaha G, Stanley RE, Steitz TA (August 2009). "Formation of the first peptide bond: the structure of EF-P bound to the 70S ribosome". Science. 325 (5943): 966–70. Bibcode:2009Sci...325..966B. doi:10.1126/science.1175800. PMC 3296453. PMID 19696344.
  4. ↑ Elgamal S, Katz A, Hersch SJ, Newsom D, White P, Navarre WW, Ibba M (August 2014). "EF-P dependent pauses integrate proximal and distal signals during translation". PLOS Genetics. 10 (8): e1004553. doi:10.1371/journal.pgen.1004553. PMC 4140641. PMID 25144653.
  5. 1 2 Hanawa-Suetsugu K, Sekine S, Sakai H, Hori-Takemoto C, Terada T, Unzai S, et al. (June 2004). "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. Bibcode:2004PNAS..101.9595H. doi:10.1073/pnas.0308667101. PMC 470720. PMID 15210970.
  6. ↑ Rossi D, Kuroshu R, Zanelli CF, Valentini SR (2013). "eIF5A and EF-P: two unique translation factors are now traveling the same road". Wiley Interdisciplinary Reviews. RNA. 5 (2): 209–22. doi:10.1002/wrna.1211. PMID 24402910. S2CID 25447826.
  7. 1 2 Park JH, Johansson HE, Aoki H, Huang BX, Kim HY, Ganoza MC, Park MH (January 2012). "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. doi:10.1074/jbc.M111.309633. PMC 3268417. PMID 22128152.
  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 (24 May 2019). "Switching the Post-translational Modification of Translation Elongation Factor EF-P". Frontiers in Microbiology. 10: 1148. doi:10.3389/fmicb.2019.01148. PMC 6544042. PMID 31178848.
  9. 1 2 Doerfel LK, Rodnina MV (November 2013). "Elongation factor P: Function and effects on bacterial fitness". Biopolymers. 99 (11): 837–45. doi:10.1002/bip.22341. hdl:11858/00-001M-0000-0013-F8DD-5. PMID 23828669.
  10. ↑ Glick BR, Ganoza MC (November 1975). "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. Bibcode:1975PNAS...72.4257G. doi:10.1073/pnas.72.11.4257. PMC 388699. PMID 1105576.
  11. ↑ Tollerson R, Witzky A, Ibba M (October 2018). "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. Bibcode:2018PNAS..11511072T. doi:10.1073/pnas.1812025115. PMC 6205485. PMID 30297417.
  12. ↑ Liljas A (October 2009). "Leaps in translational elongation". Science. 326 (5953): 677–8. doi:10.1126/science.1181511. PMID 19833922. S2CID 45692923.
  13. ↑ Ude S, Lassak J, Starosta AL, Kraxenberger T, Wilson DN, Jung K (January 2013). "Translation elongation factor EF-P alleviates ribosome stalling at polyproline stretches". Science. 339 (6115): 82–5. Bibcode:2013Sci...339...82U. doi:10.1126/science.1228985. PMID 23239623. S2CID 206544633.
This article incorporates text from the public domain Pfam and InterPro: IPR001059
This article incorporates text from the public domain Pfam and InterPro: IPR015365
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