TY - JOUR
T1 - Molecular Landscape of the Ribosome Pre-initiation Complex during mRNA Scanning
T2 - Structural Role for eIF3c and Its Control by eIF5
AU - Obayashi, Eiji
AU - Luna, Rafael E.
AU - Nagata, Takashi
AU - Martin-Marcos, Pilar
AU - Hiraishi, Hiroyuki
AU - Singh, Chingakham Ranjit
AU - Erzberger, Jan Peter
AU - Zhang, Fan
AU - Arthanari, Haribabu
AU - Morris, Jacob
AU - Pellarin, Riccardo
AU - Moore, Chelsea
AU - Harmon, Ian
AU - Papadopoulos, Evangelos
AU - Yoshida, Hisashi
AU - Nasr, Mahmoud L.
AU - Unzai, Satoru
AU - Thompson, Brytteny
AU - Aube, Eric
AU - Hustak, Samantha
AU - Stengel, Florian
AU - Dagraca, Eddie
AU - Ananbandam, Asokan
AU - Gao, Philip
AU - Urano, Takeshi
AU - Hinnebusch, Alan G.
AU - Wagner, Gerhard
AU - Asano, Katsura
N1 - Publisher Copyright:
© 2017 The Author(s)
PY - 2017/3/14
Y1 - 2017/3/14
N2 - During eukaryotic translation initiation, eIF3 binds the solvent-accessible side of the 40S ribosome and recruits the gate-keeper protein eIF1 and eIF5 to the decoding center. This is largely mediated by the N-terminal domain (NTD) of eIF3c, which can be divided into three parts: 3c0, 3c1, and 3c2. The N-terminal part, 3c0, binds eIF5 strongly but only weakly to the ribosome-binding surface of eIF1, whereas 3c1 and 3c2 form a stoichiometric complex with eIF1. 3c1 contacts eIF1 through Arg-53 and Leu-96, while 3c2 faces 40S protein uS15/S13, to anchor eIF1 to the scanning pre-initiation complex (PIC). We propose that the 3c0:eIF1 interaction diminishes eIF1 binding to the 40S, whereas 3c0:eIF5 interaction stabilizes the scanning PIC by precluding this inhibitory interaction. Upon start codon recognition, interactions involving eIF5, and ultimately 3c0:eIF1 association, facilitate eIF1 release. Our results reveal intricate molecular interactions within the PIC, programmed for rapid scanning-arrest at the start codon.
AB - During eukaryotic translation initiation, eIF3 binds the solvent-accessible side of the 40S ribosome and recruits the gate-keeper protein eIF1 and eIF5 to the decoding center. This is largely mediated by the N-terminal domain (NTD) of eIF3c, which can be divided into three parts: 3c0, 3c1, and 3c2. The N-terminal part, 3c0, binds eIF5 strongly but only weakly to the ribosome-binding surface of eIF1, whereas 3c1 and 3c2 form a stoichiometric complex with eIF1. 3c1 contacts eIF1 through Arg-53 and Leu-96, while 3c2 faces 40S protein uS15/S13, to anchor eIF1 to the scanning pre-initiation complex (PIC). We propose that the 3c0:eIF1 interaction diminishes eIF1 binding to the 40S, whereas 3c0:eIF5 interaction stabilizes the scanning PIC by precluding this inhibitory interaction. Upon start codon recognition, interactions involving eIF5, and ultimately 3c0:eIF1 association, facilitate eIF1 release. Our results reveal intricate molecular interactions within the PIC, programmed for rapid scanning-arrest at the start codon.
UR - https://www.scopus.com/pages/publications/85015194327
UR - https://www.scopus.com/pages/publications/85015194327#tab=citedBy
U2 - 10.1016/j.celrep.2017.02.052
DO - 10.1016/j.celrep.2017.02.052
M3 - Article
C2 - 28297669
AN - SCOPUS:85015194327
SN - 2211-1247
VL - 18
SP - 2651
EP - 2663
JO - Cell Reports
JF - Cell Reports
IS - 11
ER -