title: Eukaryotic translation initiation is controlled by cooperativity effects within ternary complexes of 4E-BP1, eIF4E, and the mRNA 5' cap.
abstract: Initiation is the rate-limiting step during mRNA 5' cap-dependent translation, and thus a target of a strict control in the eukaryotic cell. It is shown here by analytical ultracentrifugation and fluorescence spectroscopy that the affinity of the human translation inhibitor, eIF4E-binding protein (4E-BP1), to the translation initiation factor 4E is significantly higher when eIF4E is bound to the cap. The 4E-BP1 binding stabilizes the active eIF4E conformation and, on the other hand, can facilitate dissociation of eIF4E from the cap. These findings reveal the particular allosteric effects forming a thermodynamic cycle for the cooperative regulation of the translation initiation inhibition.
authors.affiliation: Division of Biophysics, Institute of Experimental Physics, Faculty of Physics, University of Warsaw, 93 Zwirki & Wigury St., 02-089 Warszawa, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Modrak-Wojcik
authors.forename: Michal
authors.initials: M
authors.lastname: Gorka
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Niedzwiecka
authors.forename: Konrad
authors.initials: K
authors.lastname: Zdanowski
authors.forename: Joanna
authors.initials: J
authors.lastname: Zuberek
authors.forename: Anna
authors.initials: A
authors.lastname: Niedzwiecka
authors.forename: Ryszard
authors.initials: R
authors.lastname: Stolarski
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000737:chemistry / Q000378:metabolism*; D018797:Cell Cycle Proteins; D039561:Eukaryotic Initiation Factor-4E / Q000737:chemistry / Q000378:metabolism*; D039642:Eukaryotic Initiation Factors / Q000737:chemistry / Q000378:metabolism; D031521:Fractionation, Field Flow; D006801:Humans; D008954:Models, Biological; D046912:Multiprotein Complexes / Q000737:chemistry / Q000378:metabolism; D010442:Peptide Chain Initiation, Translational / Q000502:physiology*; D010750:Phosphoproteins / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding / Q000502:physiology; D011487:Protein Conformation; D055503:Protein Multimerization / Q000502:physiology*; D012315:RNA Caps / Q000378:metabolism*; D012333:RNA, Messenger / Q000737:chemistry / Q000378:metabolism; D014461:Ultracentrifugation
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D018797:Cell Cycle Proteins; C087000:EIF4EBP1 protein, human; D039561:Eukaryotic Initiation Factor-4E; D039642:Eukaryotic Initiation Factors; D046912:Multiprotein Complexes; D010750:Phosphoproteins; D012315:RNA Caps; D012333:RNA, Messenger
keywords: 4E binding protein 1; 4E-BP1; 7-methylguanosine 5′-triphosphate; Analytical ultracentrifugation; DB; Fluorescence; SPR; TCEP; TFA; Translation initiation; dialysis buffer; eIF4E; eukaryotic initiation factor 4E; m(7)GTP; mRNA 5′cap; surface plasmon resonance; trifluoroacetic acid; tris (2-carboxyethyl) phosphine HCl