Initiation factors
Initiation factors (more precisely: translation initiation factors ) are proteins and protein complexes in the cells of all living things that are necessary for efficient translation of the mRNA and have a function during the initiation of translation. Since the initiation of the eukaryotes differs significantly from that of the prokaryotes , the participating proteins must be differentiated. Mutations in the genes that code for subunits of the eIF-2B complex are responsible for a special hereditary form of leukodystrophy (VWM).
Prokaryotic initiation factors
Prokaryotes have three proteins (IF-1, IF-2, and IF-3) that together initiate translation. They all bind to the small subunit of the ribosome . Each of these proteins has a specific function and takes on a step of initiation:
- IF-1 prevents the premature binding of tRNA to the site of the mRNA that will later form the A-site of the ribosome.
- IF-2 is a GTPase . It ensures that the initiator tRNA ( formylmethionine tRNA ) binds to the start codon . The energy released by hydrolyzing a GTP interacts with IF-1, the small subunit of the ribosome, and the initiator tRNA.
- IF-3 prevents the large subunit from binding prematurely to the small one. IF-3 binds to the small subunit as early as possible to ensure that a new translation can be initialized. It even seems to be the case that this factor supports the cleavage of the small and large subunits after translation.
Eukaryotic initiation factors
Eukaryotic initiation factors belong to many different protein families and have a multitude of functions: to unwind the mRNA, to recognize its 5'-cap structure , to regulate its binding to the ribosome , to bind the starter tRNA and to leave the complex with it the ribosome 60S subunit can perform the elongation.
About 45 genes are known in humans which code for eukaryotic initiation factors. The proteins belong to the following complexes and families:
| complex | Protein family |
Genes (HGNC) | function | |
|---|---|---|---|---|
| DEAD box helicopters, DEAH family | DHX29 | Binds to 40S near the mRNA entrance; Translation efficiency | ||
| eIF-1A | EIF1AX , EIF1AY | Helps in the separation of the ribosome subunits, binds Met-tRNA; Translation efficiency | ||
| eIF-2 | eIF-2α | EIF2S1 | Complex with GTP and initiator tRNA, later additionally with 40S, consumes GTP | |
| eIF-2β | EIF2S2 , A6NK07 , EIF5 | |||
| eIF-2G | EIF2S3 , EIF2S3L | |||
| eIF-2B | eIF-2B-α / β / δ | EIF2B1 , EIF2B2 , EIF2B4 | Complex catalyzes GTP-GDP exchange in eIF-2 . Pathology: leukodystrophy | |
| eIF-2B-γ / ε | EIF2B3 , EIF2B5 | |||
| eIF-2A | EIF2A | Allows initiation of certain special mRNA | ||
| eIF-2D | EIF2D | Deliver tRNA to the P-site of the 40S without the need for GTP. In addition, elongation factor. | ||
| eIF-3 | div. | Module A: EIF3A , EIF3B , EIF3G , EIF3I . Module B: EIF3F , EIF3H , EIF3M . Module C: EIF3C , EIF3D , EIF3E , EIF3L , EIF3K | Binds to 40S, enables binding of eIF-1/2, stimulates initiator tRNA binding and 5'-cap recognition; Ultimately facilitates the separation of the entire complex so that 60S can dock. | |
| eIF-4F | DEAD-Box-Helicases , eIF4A family | EIF4A1 , EIF4A2 | Recognizes cap structure, enables mRNA binding to ribosome, unwinds mRNA. | |
| eIF-4E | EIF4E , EIF4E1B , EIF4E2 , EIF4E3 | |||
| eIF-4G | EIF4G1 , EIF4G2 , EIF4G3 | |||
| eIF-6 | EIF6 | Binds to 60S and prevents them from docking with 40S | ||
| IF-2 | MTIF2 , EIF5B | Initiation factor in mitochondria; homologous to prokaryotic IF-2; facilitates binding of formylmethionine tRNA | ||
| IF-3 | MTIF3 | Initiation factor in mitochondria; homologous to prokaryotic IF-3; facilitates dissociation of the 55S ribosomes |
literature
- TV Pestova, VG Kolupaeva u. a .: Molecular mechanisms of translation initiation in eukaryotes. In: Proceedings of the National Academy of Sciences of the United States of America . Volume 98, Number 13, June 2001, pp. 7029-7036. doi : 10.1073 / pnas.111145798 . PMID 11416183 . PMC 34618 (free full text). (Review).
- K. Asano, L. Phan, et al. a .: A multifactor complex of eIF1, eIF2, eIF3, eIF5, and tRNA (i) Met promotes initiation complex assembly and couples GTP hydrolysis to AUG recognition. In: Cold Spring Harbor symposia on quantitative biology. Volume 66, 2001, pp. 403-415, ISSN 0091-7451 . PMID 12762043 . (Review).
- AG Hinnebusch: eIF3: a versatile scaffold for translation initiation complexes. In: Trends in biochemical sciences . Volume 31, Number 10, October 2006, pp. 553-562, ISSN 0968-0004 . doi : 10.1016 / j.tibs.2006.08.005 . PMID 16920360 . (Review).
- F. Saletta, YS Rahmanto, DR Richardson: The translational regulator eIF3a: the tricky eIF3 subunit! In: Biochimica et biophysica acta . Volume 1806, Number 2, December 2010, pp. 275-286. doi : 10.1016 / j.bbcan.2010.07.005 . PMID 20647036 . (Review).
Individual evidence
- ↑ Leucoencephalopathy with vanishing white matter. In: Online Mendelian Inheritance in Man . (English)
- ↑ James D. Watson , Tania A. Baker , Stephen P. Bell , Alexander Gann , Michael Levine , Richard Losick : Watson Molecular Biology - Das Molekulare Grundwissen der Biologie 2010, 6th edition, Pearson Studium - Biologie 2010. ISBN 3868940294 . P. 527.
- ↑ Jochen Graw , Wolfgang Hennig : Genetik 2010, 5th edition, Springer 2010. ISBN 3642049982 . Pp. 84-85.
- ↑ UniProt search result Human initiation factors ( memento of the original from December 22, 2016 in the Internet Archive ) Info: The archive link has been inserted automatically and has not yet been checked. Please check the original and archive link according to the instructions and then remove this notice.
