Eukaryotic initiation factor 4F

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Solution structure of yeast eIF4E bound to the m7G cap and a eIF4G fragment (PDB 1RF8).[1]

Eukaryotic initiation factor 4F (eIF4F) is a heterotrimeric

RNA helicase eIF4A, the cap-binding protein eIF4E, and the large "scaffold" protein eIF4G.[2][3] 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.[3]

Function

eIF4F is important for recruiting 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.[3]

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.[4]

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.

RNA helicase activity.[3]

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

eIF3 via eIF4G, while budding yeast lacks this connection.[3] Interactions between eIF4G and PABP are thought to mediate the circularization of mRNA particles.[5]

Subunit MW (kDa)[A] Isoforms Key Features
eIF4A 46 eIF4A1, eIF4A2, eIF4A3 DEAD-box RNA helicase. Binds mRNA, eIF4G, eIF4B, eIF4H, and PDCD4. Inhibited by the small molecules hippuristanol,[6] rocaglamide A (RocA),[7] and pateamine A.[8]
eIF4E 25
eIF4E1, eIF4E2, eIF4E3
 Cap-binding protein. Binds eIF4G, 4EBP1, 4EBP2 and 4EBP3.
eIF4G 175
eIF4G1, eIF4G3
 "Scaffold" protein. Binds mRNA, eIF4A, eIF4E, and PABP.

A 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 and eIF4H. The unusual isoform of eIF4G, eIF4G2 or DAP5, also appears to perform a non-canonical translation function.

Regulation

The eIF4E subunit of eIF4F is an important target of mTOR signaling through the eIF4E binding protein (4E-BP).[3] Phosphorylation of 4E-BPs by mTOR prevents their binding to eIF4E, freeing eIF4E to bind eIF4G and participate in translation initiation.[3]

See also

References

  1. PMID 14675538
    .
  2. S2CID 9201095
    .
  3. ^
    PMID 26324716
    .
  4. PMID 25742741
    .
  5. PMID 9702200
    .
  6. PMID 27335721
    .
  7. PMID 27309803
    .
  8. PMID 16337595
    .
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