Eukaryotic initiation factor 4F (eIF4F) is a heterotrimeric

protein complex A protein complex or multiprotein complex is a group of two or more associated polypeptide chains. Protein complexes are distinct from multienzyme complexes, in which multiple catalytic domains are found in a single polypeptide chain. Protein c ...

that binds the 5' cap of messenger RNAs (mRNAs) to promote

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

initiation. The eIF4F complex is composed of three non-identical subunits: the DEAD-box

RNA helicase Helicases are a class of enzymes thought to be vital to all organisms. Their main function is to unpack an organism's genetic material. Helicases are motor proteins that move directionally along a nucleic acid phosphodiester backbone, separati ...

eIF4A The eukaryotic initiation factor-4A (eIF4A) family consists of 3 closely related proteins EIF4A1, EIF4A2, and EIF4A3. These factors are required for the binding of mRNA to 40S ribosomal subunits. In addition these proteins are helicases that ...

, the cap-binding protein

eIF4E Eukaryotic translation initiation factor 4E, also known as eIF4E, is a protein that in humans is encoded by the ''EIF4E'' gene. Structure and function Most eukaryotic cellular mRNAs are blocked at their 5'-ends with the 7-methyl-guanosine f ...

, and the large "scaffold" protein

eIF4G Eukaryotic translation initiation factor 4 G (eIF4G) is a protein involved in eukaryotic translation initiation and is a component of the eIF4F cap-binding complex. Orthologs of eIF4G have been studied in multiple species, including humans, yeas ...

. The mammalian eIF4F complex was first described in 1983, and has been a major area of study into the molecular mechanisms of cap-dependent translation initiation ever since.

Function

eIF4F is important for recruiting the small ribosomal subunit (40S) to the 5' cap of mRNAs during cap-dependent translation initiation. Components of the complex are also involved in cap-independent translation initiation; for instance, certain viral proteases cleave eIF4G to remove the eIF4E-binding region, thus inhibiting cap-dependent translation.

Structure

Structures of eIF4F components have been solved individually and as partial complexes by a variety of methods, but no complete structure of eIF4F is currently available.

Subunits

In mammals, the eIF4E•G•A trimeric complex can be directly purified from cells, while only the two subunit eIF4E•G can be purified from yeast cells.

binds the m⁷G 5' cap and the eIF4G scaffold, connecting the mRNA 5' terminus to a hub of other initiation factors and mRNA. The interaction of eIF4G•A is thought to guide the formation of a single-stranded RNA landing pad for the

43S preinitiation complex The 43S preinitiation complex (43S PIC) is a ribonucleoprotein complex that exists during an early step of eukaryotic translation initiation. The 43S PIC contains the small ribosomal subunit (40S) bound by the initiation factors eIF1, eIF1A, eIF3 ...

(43S PIC) via eIF4A's

activity. The eIF4F proteins interact with a number of different binding partners, and there are multiple genetic isoforms of

, and

in the human genome. In mammals, eIF4F is bridged to the 40S ribosomal subunit by

eIF3 Eukaryotic initiation factor 3 (eIF3) is a multiprotein complex that functions during the initiation phase of eukaryotic translation. It is essential for most forms of cap-dependent and cap-independent translation initiation. In humans, eIF3 co ...

via

, while budding yeast lacks this connection. Interactions between

and PABP are thought to mediate the circularization of mRNA particles. Approximate molecular weight for human proteins. In addition to the major proteins encompassing the eIF4F trimer, the eIF4F complex functionally interacts with proteins including

eIF4B Eukaryotic translation initiation factor 4B is a protein that in humans is encoded by the ''EIF4B'' gene. Interactions eIF4B has been shown to interact with and stimulate the activity of eIF4A and bind to the eIF3 complex through the eIF3A sub ...

and

eIF4H Eukaryotic translation initiation factor 4H is a protein that in humans is encoded by the ''EIF4H'' gene. This gene encodes one of the translation initiation factors, which function to stimulate the initiation of protein synthesis at the level of ...

. The unusual isoform of eIF4G,

eIF4G2 Eukaryotic translation initiation factor 4 gamma 2 (also called p97, NAT1, and DAP-5) is a protein that in humans is encoded by the ''EIF4G2'' gene. Function Translation initiation is mediated by specific recognition of the cap structure by euk ...

or DAP5, also appears to perform a non-canonical translation function.

Regulation

The

subunit of eIF4F is an important target of

mTOR The mammalian target of sirolimus, rapamycin (mTOR), also referred to as the mechanistic target of rapamycin, and sometimes called FK506-binding protein 12-rapamycin-associated protein 1 (FRAP1), is a kinase that in humans is encoded by the ''MT ...

signaling through the eIF4E binding protein (4E-BP). Phosphorylation of 4E-BPs by mTOR prevents their binding to eIF4E, freeing eIF4E to bind eIF4G and participate in translation initiation.

References

* * * * {{DEFAULTSORT:Eukaryotic Translation Protein biosynthesis Molecular biology Gene expression Protein complexes RNA-binding proteins

Function

Structure

Subunits

Regulation

See also

References