General Information

Database Accession: DI1010046

Name: 4E-BP1 peptide bound to EIF4E

PDB ID: 1ej4 PDB

Experimental method: X-ray (2.25 Å)

Source organism: Homo sapiens / Mus musculus

Proof of disorder: Confirmed

K_d: 5.00×10^-08 M PubMed

Primary publication of the structure:

Marcotrigiano J, Gingras AC, Sonenberg N, Burley SK
Cap-dependent translation initiation in eukaryotes is regulated by a molecular mimic of eIF4G.
(1999) Mol. Cell 3: 707-16

PMID: 10394359 PubMed

Abstract:

eIF4G uses a conserved Tyr-X-X-X-X-Leu-phi segment (where X is variable and phi is hydrophobic) to recognize eIF4E during cap-dependent translation initiation in eukaryotes. High-resolution X-ray crystallography and complementary biophysical methods have revealed that this eIF4E recognition motif undergoes a disorder-to-order transition, adopting an L-shaped, extended chain/alpha-helical conformation when it interacts with a phylogenetically invariant portion of the convex surface of eIF4E. Inhibitors of translation initiation known as eIF4E-binding proteins (4E-BPs) contain similar eIF4E recognition motifs. These molecules are molecular mimics of eIF4G, which act by occupying the same binding site on the convex dorsum of eIF4E and blocking assembly of the translation machinery. The implications of our results for translation initiation are discussed in detail, and a molecular mechanism for relief of translation inhibition following phosphorylation of the 4E-BPs is proposed.

Function and Biology Annotations from the GeneOntology database. Only terms that fit at least two of the interacting proteins are shown.

Molecular function:

enzyme binding Interacting selectively and non-covalently with any enzyme. GeneOntology

translation initiation factor binding Interacting selectively and non-covalently with a translation initiation factor, any polypeptide factor involved in the initiation of ribosome-mediated translation. GeneOntology

Biological process:

G1/S transition of mitotic cell cycle The mitotic cell cycle transition by which a cell in G1 commits to S phase. The process begins with the build up of G1 cyclin-dependent kinase (G1 CDK), resulting in the activation of transcription of G1 cyclins. The process ends with the positive feedback of the G1 cyclins on the G1 CDK which commits the cell to S phase, in which DNA replication is initiated. GeneOntology

negative regulation of translation Any process that stops, prevents, or reduces the frequency, rate or extent of the chemical reactions and pathways resulting in the formation of proteins by the translation of mRNA. GeneOntology

lung development The process whose specific outcome is the progression of the lung over time, from its formation to the mature structure. In all air-breathing vertebrates the lungs are developed from the ventral wall of the oesophagus as a pouch which divides into two sacs. In amphibians and many reptiles the lungs retain very nearly this primitive sac-like character, but in the higher forms the connection with the esophagus becomes elongated into the windpipe and the inner walls of the sacs become more and more divided, until, in the mammals, the air spaces become minutely divided into tubes ending in small air cells, in the walls of which the blood circulates in a fine network of capillaries. In mammals the lungs are more or less divided into lobes, and each lung occupies a separate cavity in the thorax. GeneOntology

positive regulation of mitotic cell cycle Any process that activates or increases the rate or extent of progression through the mitotic cell cycle. GeneOntology

cellular response to dexamethasone stimulus Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a dexamethasone stimulus. GeneOntology

response to stress Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a disturbance in organismal or cellular homeostasis, usually, but not necessarily, exogenous (e.g. temperature, humidity, ionizing radiation). GeneOntology

translational initiation The process preceding formation of the peptide bond between the first two amino acids of a protein. This includes the formation of a complex of the ribosome, mRNA, and an initiation complex that contains the first aminoacyl-tRNA. GeneOntology

Cellular component:

cytosol The part of the cytoplasm that does not contain organelles but which does contain other particulate matter, such as protein complexes. GeneOntology

protein complex A stable macromolecular complex composed (only) of two or more polypeptide subunits along with any covalently attached molecules (such as lipid anchors or oligosaccharide) or non-protein prosthetic groups (such as nucleotides or metal ions). Prosthetic group in this context refers to a tightly bound cofactor. The component polypeptide subunits may be identical. GeneOntology

membrane-bounded organelle Organized structure of distinctive morphology and function, bounded by a single or double lipid bilayer membrane. Includes the nucleus, mitochondria, plastids, vacuoles, and vesicles. Excludes the plasma membrane. GeneOntology

Structure Summary Structural annotations of the participating protein chains.

Entry contents: 2 distinct polypeptide molecules

Chains: B, A

Notes: No modifications of the original PDB file.

Chain B

Name: Eukaryotic translation initiation factor 4E-binding protein 1 Disordered Confirmed

Source organism: Homo sapiens

Length: 14 residues

Sequence:Sequence according to PDB SEQRESRIIYDRKFLMECRN

UniProtKB AC: Q13541 (positions: 51-64) UniProt Coverage: 11.9%

UniRef90 AC: UniRef90_Q13541 (positions: 51-64) UniRef90

Chain A

Name: Eukaryotic translation initiation factor 4E Ordered

Source organism: Mus musculus

Length: 186 residues

Sequence:Sequence according to PDB SEQRESEHYIKHPLQNRWALWFFKNDKSKTWQANLRLISKFDTVEDFWALYNHIQLSSNLMPGCDYSLFKDGIEPMWEDEKNKRGGRWLITLNKQQRRSDLDRFWLETLLCLIGESFDDYSDDVCGAVVNVRAKGDKIAIWTTECENRDAVTHIGRVYKERLGLPPKIVIGYQSHADTATKSGSTTKNRFVV

UniProtKB AC: P63073 (positions: 32-217) UniProt Coverage: 85.7%

UniRef90 AC: UniRef90_P63073 (positions: 32-217) UniRef90

Evidence Evidence demonstrating that the participating proteins are unstructured prior to the interaction and their folding is coupled to binding.

Chain B: Disordered Confirmed

The interacting region of 4E-BP1 has been shown to be intrinsically disordered (PMID: 9684899 and PMID: 10394359). The 1-118 region described in IDEAL entry IID00170 covers 100% of the sequence present in the structure. The protein region involved in the interaction contains a known functional linear motif (LIG_eIF4E_1).

Chain A: Ordered

The IF4E domain involved in the interaction is known to adopt a stable structure in isolation (see Pfam domain PF01652). A solved monomeric structure of the domain from a homologous protein is represented by PDB ID 3tf2.

Related Structure(s) Structures from the PDB that contain the same number of proteins, and the proteins from the two structures show a sufficient degree of pairwise similarity, i.e. they belong to the same UniRef90 cluster (the full proteins exhibit at least 90% sequence identity) and convey roughly the same region to their respective interactions (the two regions from the two proteins share a minimum of 70% overlap).

There are 2 related structures in the Protein Data Bank:

• 1ejh
• 5bxv

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