TY - JOUR
T1 - Molecular architecture of the 40S · eIF1 · eIF3 translation initiation complex
AU - Erzberger, Jan P.
AU - Stengel, Florian
AU - Pellarin, Riccardo
AU - Zhang, Suyang
AU - Schaefer, Tanja
AU - Aylett, Christopher H.S.
AU - Cimermančič, Peter
AU - Boehringer, Daniel
AU - Sali, Andrej
AU - Aebersold, Ruedi
AU - Ban, Nenad
N1 - Funding Information:
We would like to thank F. Tritschler, B. Greber, M. Leibundgut, N. Schmitz, S. Klinge, S.J. Kim, B. Webb, D. Russel, M. Bonomi, Y. Spill, and members from the Ban, Sali, and Aebersold labs for helpful discussions and C. Weirich and C. Greenberg for critical reading of the manuscript. We are indebted to P. Tittman at the ETH scientific center for optical and electron microscopy and to the staff at the Swiss Light Source. This work was supported by an EMBO postdoctoral fellowship (to J.P.E.), a Sir Henry Wellcome Fellowship (Grant 095951 to F.S.), an ETH postdoctoral fellowship (to C.S.H.A.), and a HHMI Predoctoral Fellowship (to P.C.). We acknowledge support from Swiss National Science Foundation (SNSF) grants PA00P3_139727 and PBZHP3-133388 (to R.P.), NIH grants U54 GM103511 and R01 GM083960 (to A.S.), funding from ETH Zurich, SystemsX, and ERC advanced grant 233226 (to R.A.), and support from the SNSF, the National Center of Excellence in Research Structural Biology and RNA and Disease programs, and ERC grant 250071 (to N.B.).
PY - 2014/8/28
Y1 - 2014/8/28
N2 - 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. 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 40SâeIF1 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.
AB - 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. 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 40SâeIF1 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.
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U2 - 10.1016/j.cell.2014.07.044
DO - 10.1016/j.cell.2014.07.044
M3 - Article
C2 - 25171412
AN - SCOPUS:84907323467
SN - 0092-8674
VL - 158
SP - 1123
EP - 1135
JO - Cell
JF - Cell
IS - 5
ER -