Reconfiguration of yeast 40S ribosomal subunit domains by the translation initiation multifactor complex.
In the process of protein synthesis, the small (40S) subunit of the eukaryotic ribosome is recruited to the capped 5' end of the mRNA, from which point it scans along the 5' untranslated region in search of a start codon. However, the 40S subunit alone is not capable of functional association with cellular mRNA species; it has to be prepared for the recruitment and scanning steps by interactions with a group of eukaryotic initiation factors (eIFs). In budding yeast, an important subset of these factors (1, 2, 3, and 5) can form a multifactor complex (MFC). Here, we describe cryo-EM reconstructions of the 40S subunit, of the MFC, and of 40S complexes with MFC factors plus eIF1A. These studies reveal the positioning of the core MFC on the 40S subunit, and show how eIF-binding induces mobility in the head and platform and reconfigures the head-platform-body relationship. This is expected to increase the accessibility of the mRNA channel, thus enabling the 40S subunit to convert to a recruitment-competent state.
Gilbert
Robert J C
RJ
Division of Structural Biology, Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, United Kingdom.
Gordiyenko
Yulya
Y
von der Haar
Tobias
T
Sonnen
Andreas F-P
AF
Hofmann
Gregor
G
Nardelli
Maria
M
Stuart
David I
DI
McCarthy
John E G
JE
D020121:5' Untranslated Regions; D018387:Codon, Initiator; D020285:Cryoelectron Microscopy; D015977:Eukaryotic Initiation Factor-1 / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure; D015852:Eukaryotic Initiation Factor-2 / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure; D039621:Eukaryotic Initiation Factor-3 / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure; D040061:Eukaryotic Initiation Factor-5 / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure; D008956:Models, Chemical; D008958:Models, Molecular; D011485:Protein Binding; D014176:Protein Biosynthesis; D017433:Protein Structure, Secondary; D021122:Protein Subunits; D012331:RNA, Fungal / Q000235:genetics / Q000378:metabolism / Q000648:ultrastructure; D012333:RNA, Messenger / Q000378:metabolism; D012270:Ribosomes / Q000737:chemistry* / Q000378:metabolism / Q000648:ultrastructure; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism
D020121:5' Untranslated Regions; D018387:Codon, Initiator; D015977:Eukaryotic Initiation Factor-1; D015852:Eukaryotic Initiation Factor-2; D039621:Eukaryotic Initiation Factor-3; D040061:Eukaryotic Initiation Factor-5; D021122:Protein Subunits; D012331:RNA, Fungal; D012333:RNA, Messenger