7qp6
From Proteopedia
Structure of the human 48S initiation complex in open state (h48S AUG open)
Structural highlights
FunctionEIF3B_HUMAN Component of the eukaryotic translation initiation factor 3 (eIF-3) complex, which is required for several steps in the initiation of protein synthesis. The eIF-3 complex associates with the 40S ribosome and facilitates the recruitment of eIF-1, eIF-1A, eIF-2:GTP:methionyl-tRNAi and eIF-5 to form the 43S preinitiation complex (43S PIC). The eIF-3 complex stimulates mRNA recruitment to the 43S PIC and scanning of the mRNA for AUG recognition. The eIF-3 complex is also required for disassembly and recycling of post-termination ribosomal complexes and subsequently prevents premature joining of the 40S and 60S ribosomal subunits prior to initiation.[1] Publication Abstract from PubMedSelection of the translation start codon is a key step during protein synthesis in human cells. We obtained cryo-EM structures of human 48S initiation complexes and characterized the intermediates of codon recognition by kinetic methods using eIF1A as a reporter. Both approaches capture two distinct ribosome populations formed on an mRNA with a cognate AUG codon in the presence of eIF1, eIF1A, eIF2-GTP-Met-tRNAiMet and eIF3. The 'open' 40S subunit conformation differs from the human 48S scanning complex and represents an intermediate preceding the codon recognition step. The 'closed' form is similar to reported structures of complexes from yeast and mammals formed upon codon recognition, except for the orientation of eIF1A, which is unique in our structure. Kinetic experiments show how various initiation factors mediate the population distribution of open and closed conformations until 60S subunit docking. Our results provide insights into the timing and structure of human translation initiation intermediates and suggest the differences in the mechanisms of start codon selection between mammals and yeast. Conformational rearrangements upon start codon recognition in human 48S translation initiation complex.,Yi SH, Petrychenko V, Schliep JE, Goyal A, Linden A, Chari A, Urlaub H, Stark H, Rodnina MV, Adio S, Fischer N Nucleic Acids Res. 2022 May 20;50(9):5282-5298. doi: 10.1093/nar/gkac283. PMID:35489072[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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Categories: Homo sapiens | Large Structures | Adio S | Chari A | Fischer N | Goyal A | Linden A | Petrychenko V | Rodnina MV | Schliep JE | Stark H | Urlaub H | Yi S-H
