Structural roles for human translation factor eIF3 in initiation of protein synthesis.
Protein synthesis in mammalian cells requires initiation factor eIF3, a approximately 750-kilodalton complex that controls assembly of 40S ribosomal subunits on messenger RNAs (mRNAs) bearing either a 5'-cap or an internal ribosome entry site (IRES). Cryo-electron microscopy reconstructions show that eIF3, a five-lobed particle, interacts with the hepatitis C virus (HCV) IRES RNA and the 5'-cap binding complex eIF4F via the same domain. Detailed modeling of eIF3 and eIF4F onto the 40S ribosomal subunit reveals that eIF3 uses eIF4F or the HCV IRES in structurally similar ways to position the mRNA strand near the exit site of 40S, promoting initiation complex assembly.
Siridechadilok
Bunpote
B
Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA.
Fraser
Christopher S
CS
Hall
Richard J
RJ
Doudna
Jennifer A
JA
Nogales
Eva
E
D001665:Binding Sites; D039621:Eukaryotic Initiation Factor-3 / Q000737:chemistry / Q000502:physiology* / Q000648:ultrastructure; D039562:Eukaryotic Initiation Factor-4F / Q000378:metabolism; D006367:HeLa Cells; D016174:Hepacivirus / Q000235:genetics; D006801:Humans; D008958:Models, Molecular; D011485:Protein Binding; D014176:Protein Biosynthesis / Q000502:physiology*; D011487:Protein Conformation; D012333:RNA, Messenger / Q000378:metabolism; D012367:RNA, Viral / Q000378:metabolism; D012270:Ribosomes / Q000378:metabolism; D013329:Structure-Activity Relationship
D039621:Eukaryotic Initiation Factor-3; D039562:Eukaryotic Initiation Factor-4F; D012333:RNA, Messenger; D012367:RNA, Viral