Abstract
SummaryEukaryotic translation initiation requires the recruitment of the large, multiprotein eIF3 complex to the 40S ribosomal subunit. We present X-ray structures of all major components of the minimal, six-subunit Saccharomyces cerevisiae eIF3 core. These structures, together with electron microscopy reconstructions, cross-linking coupled to mass spectrometry, and integrative structure modeling, allowed us to position and orient all eIF3 components on the 40S⋅eIF1 complex, revealing an extended, modular arrangement of eIF3 subunits. Yeast eIF3 engages 40S in a clamp-like manner, fully encircling 40S to position key initiation factors on opposite ends of the mRNA channel, providing a platform for the recruitment, assembly, and regulation of the translation initiation machinery. The structures of eIF3 components reported here also have implications for understanding the architecture of the mammalian 43S preinitiation complex and the complex of eIF3, 40S, and the hepatitis C internal ribosomal entry site RNA.
Highlights
Protein synthesis is catalyzed by the ribosome in a process that consists of initiation, elongation, and termination
Eukaryotic translation initiation requires the recruitment of the large, multiprotein eIF3 complex to the 40S ribosomal subunit
We present X-ray structures of all major components of the minimal, six-subunit Saccharomyces cerevisiae eIF3 core
Summary
Protein synthesis is catalyzed by the ribosome in a process that consists of initiation, elongation, and termination. Eukaryotes, in contrast, require at least 25 different polypeptides assembled into eight eukaryotic initiation factors (eIFs) to initiate protein synthesis and employ a complex scanning mechanism to probe the 50 leader sequences of mRNA for the correct start site (Hinnebusch, 2011, 2014; Jackson et al, 2010; Voigts-Hoffmann et al, 2012). Eukaryotic translation initiation begins with the cooperative assembly of the 43S preinitiation complex (PIC), composed of the eIF2/GTP/Met-tRNAi ternary complex (TC), eIF1, eIF1A, eIF5, and eIF3 on the 40S ribosomal subunit. Within the 48S PIC, eIF1, eIF1A, eIF3, and eIF4G promote the accurate scanning of the mRNA leader region (Hinnebusch, 2011, 2014) and ensure the proper recognition and pairing of the start codon with Met-tRNAi
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