Database Accession: DI1010046
Name: 4E-BP1 peptide bound to EIF4E
PDB ID: 1ej4
Experimental method: X-ray (2.25 Å)
Source organism: Homo sapiens / Mus musculus
Proof of disorder:
Kd: 5.00×10-08 M
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
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.
enzyme binding Interacting selectively and non-covalently with any enzyme.
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.
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.
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.
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.
positive regulation of mitotic cell cycle Any process that activates or increases the rate or extent of progression through the mitotic cell cycle.
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.
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).
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.
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.
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.
Entry contents: 2 distinct polypeptide molecules
Chains: B, A
Notes: No modifications of the original PDB file.
Name: Eukaryotic translation initiation factor 4E-binding protein 1
Source organism: Homo sapiens
Length: 14 residues
Sequence:Sequence according to PDB SEQRESRIIYDRKFLMECRN
UniProtKB AC: Q13541 (positions: 51-64)Coverage: 11.9%
UniRef90 AC: UniRef90_Q13541 (positions: 51-64)
Name: Eukaryotic translation initiation factor 4E
Source organism: Mus musculus
Length: 186 residues
Sequence:Sequence according to PDB SEQRESEHYIKHPLQNRWALWFFKNDKSKTWQANLRLISKFDTVEDFWALYNHIQLSSNLMPGCDYSLFKDGIEPMWEDEKNKRGGRWLITLNKQQRRSDLDRFWLETLLCLIGESFDDYSDDVCGAVVNVRAKGDKIAIWTTECENRDAVTHIGRVYKERLGLPPKIVIGYQSHADTATKSGSTTKNRFVV
UniProtKB AC: P63073 (positions: 32-217)Coverage: 85.7%
UniRef90 AC: UniRef90_P63073 (positions: 32-217)
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).
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.