title: Human translation initiation factor eIF4G1 possesses a low-affinity ATP binding site facing the ATP-binding cleft of eIF4A in the eIF4G/eIF4A complex.
abstract: Eukaryotic translation initiation factor 4G (eIF4G) plays a crucial role in translation initiation, serving as a scaffolding protein binding several other initiation factors, other proteins, and RNA. Binding of eIF4G to the ATP-dependent RNA helicase eukaryotic translation initiation factor 4A (eIF4A) enhances the activity of eIF4A in solution and in crowded environments. Previously, this activity enhancement was solely attributed to eIF4G, conferring a closed, active conformation upon eIF4A. Here we show that eIF4G contains a low-affinity binding site at the entrance to the ATP-binding cleft on eIF4A, suggesting that regulation of the local ATP concentration may be an additional reason for the enhancement in activity.
authors.affiliation: Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School , Longwood Avenue, Boston, Massachusetts 02115, United States.
authors.forename: Sabine R
authors.initials: SR
authors.lastname: Akabayov
authors.forename: Barak
authors.initials: B
authors.lastname: Akabayov
authors.forename: Gerhard
authors.initials: G
authors.lastname: Wagner
mesh_terms: D000255:Adenosine Triphosphate / Q000737:chemistry / Q000378:metabolism*; D001665:Binding Sites; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000378:metabolism; D039601:Eukaryotic Initiation Factor-4A / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*; D039603:Eukaryotic Initiation Factor-4G / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D005656:Fungal Proteins / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D042541:Intracellular Space; D007700:Kinetics; D008274:Magnesium / Q000737:chemistry / Q000378:metabolism*; D008345:Manganese / Q000737:chemistry / Q000378:metabolism; D008958:Models, Molecular; D019906:Nuclear Magnetic Resonance, Biomolecular; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*; D012995:Solubility; D056928:X-Ray Absorption Spectroscopy
chemical_list: C113920:EIF4G1 protein, human; D004791:Enzyme Inhibitors; D039603:Eukaryotic Initiation Factor-4G; D005656:Fungal Proteins; D011994:Recombinant Proteins; D029701:Saccharomyces cerevisiae Proteins; C107740:TIF4631 protein, S cerevisiae; D008345:Manganese; D000255:Adenosine Triphosphate; D039601:Eukaryotic Initiation Factor-4A; D008274:Magnesium