Elongation factor P

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Elongation factor P (EF-P) KOW-like domain
PDB 1iz6 EBI.jpg
crystal structure of translation initiation factor 5a from pyrococcus horikoshii
Identifiers
SymbolEFP_N
Pfam PF08207
Pfam clan CL0107
InterPro IPR013185
PROSITE PDOC00981
Available protein structures:
Pfam   structures / ECOD  
PDB RCSB PDB; PDBe; PDBj
PDBsum structure summary
Elongation factor P (EF-P) OB domain
PDB 1ueb EBI.jpg
crystal structure of translation elongation factor p from thermus thermophilus hb8
Identifiers
SymbolEFP
Pfam PF01132
Pfam clan CL0021
InterPro IPR001059
PROSITE PDOC00981
CDD cd04470
Available protein structures:
Pfam   structures / ECOD  
PDB RCSB PDB; PDBe; PDBj
PDBsum structure summary
Elongation factor P, C-terminal
PDB 1ueb EBI.jpg
crystal structure of translation elongation factor p from thermus thermophilus hb8
Identifiers
SymbolElong-fact-P_C
Pfam PF09285
InterPro IPR015365
SCOP2 1ueb / SCOPe / SUPFAM
CDD cd05794
Available protein structures:
Pfam   structures / ECOD  
PDB RCSB PDB; PDBe; PDBj
PDBsum structure 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.

Contents

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. [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 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

Related Research Articles

<span class="mw-page-title-main">Ribosome</span> Synthesizes proteins in cells

Ribosomes are macromolecular machines, found within all cells, that perform biological protein synthesis. Ribosomes link amino acids together in the order specified by the codons of messenger RNA molecules to form polypeptide chains. Ribosomes consist of two major components: the small and large ribosomal subunits. Each subunit consists of one or more ribosomal RNA molecules and many ribosomal proteins. The ribosomes and associated molecules are also known as the translational apparatus.

<span class="mw-page-title-main">Translation (biology)</span> Cellular process of protein synthesis

In biology, translation is the process in living cells in which proteins are produced using RNA molecules as templates. The generated protein is a sequence of amino acids. This sequence is determined by the sequence of nucleotides in the RNA. The nucleotides are considered three at a time. Each such triple results in addition of one specific amino acid to the protein being generated. The matching from nucleotide triple to amino acid is called the genetic code. The translation is performed by a large complex of functional RNA and proteins called ribosomes. The entire process is called gene expression.

The peptidyl transferase is an aminoacyltransferase as well as the primary enzymatic function of the ribosome, which forms peptide bonds between adjacent amino acids using tRNAs during the translation process of protein biosynthesis. The substrates for the peptidyl transferase reaction are two tRNA molecules, one bearing the growing peptide chain and the other bearing the amino acid that will be added to the chain. The peptidyl chain and the amino acids are attached to their respective tRNAs via ester bonds to the O atom at the CCA-3' ends of these tRNAs. Peptidyl transferase is an enzyme that catalyzes the addition of an amino acid residue in order to grow the polypeptide chain in protein synthesis. It is located in the large ribosomal subunit, where it catalyzes the peptide bond formation. It is composed entirely of RNA. The alignment between the CCA ends of the ribosome-bound peptidyl tRNA and aminoacyl tRNA in the peptidyl transferase center contribute to its ability to catalyze these reactions. This reaction occurs via nucleophilic displacement. The amino group of the aminoacyl tRNA attacks the terminal carboxyl group of the peptidyl tRNA. Peptidyl transferase activity is carried out by the ribosome. Peptidyl transferase activity is not mediated by any ribosomal proteins but by ribosomal RNA (rRNA), a ribozyme. Ribozymes are the only enzymes which are not made up of proteins, but ribonucleotides. All other enzymes are made up of proteins. This RNA relic is the most significant piece of evidence supporting the RNA World hypothesis.

Bacterial translation is the process by which messenger RNA is translated into proteins in bacteria.

Eukaryotic translation is the biological process by which messenger RNA is translated into proteins in eukaryotes. It consists of four phases: initiation, elongation, termination, and recapping.

A release factor is a protein that allows for the termination of translation by recognizing the termination codon or stop codon in an mRNA sequence. They are named so because they release new peptides from the ribosome.

<span class="mw-page-title-main">Elongation factor</span> Proteins functioning in translation

Elongation factors are a set of proteins that function at the ribosome, during protein synthesis, to facilitate translational elongation from the formation of the first to the last peptide bond of a growing polypeptide. Most common elongation factors in prokaryotes are EF-Tu, EF-Ts, EF-G. Bacteria and eukaryotes use elongation factors that are largely homologous to each other, but with distinct structures and different research nomenclatures.

<span class="mw-page-title-main">EF-Tu</span> Prokaryotic elongation factor

EF-Tu is a prokaryotic elongation factor responsible for catalyzing the binding of an aminoacyl-tRNA (aa-tRNA) to the ribosome. It is a G-protein, and facilitates the selection and binding of an aa-tRNA to the A-site of the ribosome. As a reflection of its crucial role in translation, EF-Tu is one of the most abundant and highly conserved proteins in prokaryotes. It is found in eukaryotic mitochondria as TUFM.

A bacterial initiation factor (IF) is a protein that stabilizes the initiation complex for polypeptide translation.

<span class="mw-page-title-main">Eukaryotic translation termination factor 1</span> Protein-coding gene in the species Homo sapiens

Eukaryotic translation termination factor1 (eRF1), also referred to as TB3-1 or SUP45L1, is a protein that is encoded by the ERF1 gene. In Eukaryotes, eRF1 is an essential protein involved in stop codon recognition in translation, termination of translation, and nonsense mediated mRNA decay via the SURF complex.

Elongation factor 4 (EF-4) is an elongation factor that is thought to back-translocate on the ribosome during the translation of RNA to proteins. It is found near-universally in bacteria and in eukaryotic endosymbiotic organelles including the mitochondria and the plastid. Responsible for proofreading during protein synthesis, EF-4 is a recent addition to the nomenclature of bacterial elongation factors.

<span class="mw-page-title-main">Prokaryotic large ribosomal subunit</span>

50S is the larger subunit of the 70S ribosome of prokaryotes, i.e. bacteria and archaea. It is the site of inhibition for antibiotics such as macrolides, chloramphenicol, clindamycin, and the pleuromutilins. It includes the 5S ribosomal RNA and 23S ribosomal RNA.

<span class="mw-page-title-main">23S ribosomal RNA</span> A component of the large subunit of the prokaryotic ribosome

The 23S rRNA is a 2,904 nucleotide long component of the large subunit (50S) of the bacterial/archean ribosome and makes up the peptidyl transferase center (PTC). The 23S rRNA is divided into six secondary structural domains titled I-VI, with the corresponding 5S rRNA being considered domain VII. The ribosomal peptidyl transferase activity resides in domain V of this rRNA, which is also the most common binding site for antibiotics that inhibit translation, making it a target for ribosomal engineering. A well-known member of this antibiotic class, chloramphenicol, acts by inhibiting peptide bond formation, with recent 3D-structural studies showing two different binding sites depending on the species of ribosome. Numerous mutations in domains of the 23S rRNA with Peptidyl transferase activity have resulted in antibiotic resistance. 23S rRNA genes typically have higher sequence variations, including insertions and/or deletions, compared to other rRNAs.

<span class="mw-page-title-main">EIF5A</span> Protein-coding gene in humans

Eukaryotic translation initiation factor 5A-1 is a protein that in humans is encoded by the EIF5A gene.

<span class="mw-page-title-main">EF-G</span> Prokaryotic elongation factor

EF-G is a prokaryotic elongation factor involved in protein translation. As a GTPase, EF-G catalyzes the movement (translocation) of transfer RNA (tRNA) and messenger RNA (mRNA) through the ribosome.

<span class="mw-page-title-main">Protein synthesis inhibitor</span> Inhibitors of translation

A protein synthesis inhibitor is a compound that stops or slows the growth or proliferation of cells by disrupting the processes that lead directly to the generation of new proteins.

EF-Ts is one of the prokaryotic elongation factors. It is found in human mitochondria as TSFM. It is similar to eukaryotic EF-1B.

The P-site is the second binding site for tRNA in the ribosome. The other two sites are the A-site (aminoacyl), which is the first binding site in the ribosome, and the E-site (exit), the third. During protein translation, the P-site holds the tRNA which is linked to the growing polypeptide chain. When a stop codon is reached, the peptidyl-tRNA bond of the tRNA located in the P-site is cleaved releasing the newly synthesized protein. During the translocation step of the elongation phase, the mRNA is advanced by one codon, coupled to movement of the tRNAs from the ribosomal A to P and P to E sites, catalyzed by elongation factor EF-G.

In molecular biology, VAR1 protein domain, otherwise known as variant protein 1, is a ribosomal protein that forms part of the small ribosomal subunit in yeast mitochondria. Mitochondria possess their own ribosomes responsible for the synthesis of a small number of proteins encoded by the mitochondrial genome. VAR1 is the only protein in the yeast mitochondrial ribosome to be encoded in the mitochondria - the remaining approximately 80 ribosomal proteins are encoded in the nucleus. VAR1 along with 15S rRNA are necessary for the formation of mature 37S subunits.

Ribosomal L28e protein family is a family of evolutionarily related proteins. Members include 60S ribosomal protein L28.

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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