2jgb
STRUCTURE OF HUMAN EIF4E HOMOLOGOUS PROTEIN 4EHP WITH M7GTP
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OverviewOverview
All eukaryotic cellular mRNAs contain a 5' m(7)GpppN cap. In addition to, conferring stability to the mRNA, the cap is required for pre-mRNA, splicing, nuclear export and translation by providing an anchor point for, protein binding. In translation, the interaction between the cap and the, eukaryotic initiation factor 4E (eIF4E) is important in the recruitment of, the mRNAs to the ribosome. Human 4EHP (h4EHP) is a homologue of eIF4E., Like eIF4E it is able to bind the cap but it appears to play a different, cellular role, possibly being involved in the fine-tuning of protein, expression levels. Here we use X-ray crystallography and isothermal, titration calorimetry (ITC) to investigate further the binding of cap, analogues and peptides to h4EHP. m(7)GTP binds to 4EHP 200-fold more, weakly than it does to eIF4E with the guanine base sandwiched by a, tyrosine and a tryptophan instead of two tryptophan residues as seen in, eIF4E. The tyrosine resides on a loop that is longer in h4EHP than in, eIF4E. The consequent conformational difference between the proteins, allows the tyrosine to mimic the six-membered ring of the tryptophan in, eIF4E and adopt an orientation that is similar to that seen for equivalent, residues in other non-homologous cap-binding proteins. In the absence of, ligand the binding site is incompletely formed with one of the aromatic, residues being disordered and the side-chain of the other adopting a novel, conformation. A peptide derived from the eIF4E inhibitory protein, 4E-BP1, binds h4EHP 100-fold less strongly than eIF4E but in a similar manner., Overall the data, combined with sequence analyses of 4EHP from, evolutionary diverse species, strongly support the hypothesis that 4EHP, plays a physiological role utilizing both cap-binding and protein-binding, functions but which is distinct from eIF4E.
About this StructureAbout this Structure
2JGB is a Protein complex structure of sequences from Homo sapiens with as ligand. Known structural/functional Site: . Full crystallographic information is available from OCA.
ReferenceReference
Structures of the human eIF4E homologous protein, h4EHP, in its m7GTP-bound and unliganded forms., Rosettani P, Knapp S, Vismara MG, Rusconi L, Cameron AD, J Mol Biol. 2007 May 4;368(3):691-705. Epub 2007 Feb 20. PMID:17368478
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