28ZU

human 48S PIC with Kozak mRNA and eIF1A W70A mutant

This is a non-PDB format compatible entry.

Summary for 28ZU

• Entry DOI: 10.2210/pdb28zu/pdb
• EMDB information: 57004
• Descriptor: 18S ribosomal RNA, 40S ribosomal protein S23, 40S ribosomal protein S26, ... (47 entities in total)
• Functional Keywords: translation initiation, 48s pic, human, ribosome
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 41
• Total formula weight: 1420479.99

Authors

von Loeffelholz, O.,Barchet, C.,Klaholz, B. (deposition date: 2026-03-03, release date: 2026-06-10, Last modification date: 2026-07-22)

Primary citation

von Loeffelholz, O.,Barchet, C.,Holvec, S.,Abou Ramadan, A.,Protuc, C.,Maglott-Roth, A.,de Silva, S.N.T.,Hazemann, I.,Klaholz, B.P.
Translation initiation by the Kozak mRNA sequence is based on a conformational readout on the ribosome.
Nat Commun, 2026

PubMed Abstract: The recognition mechanism of Kozak mRNA, typically comprising purines in the -3 and +4 positions flanking the AUG start codon, has remained enigmatic for decades. To address this fundamental function in eukaryotes during translation initiation, we analysed several cryo-EM structures of human 48S preinitiation complexes with mRNA sequences differing in Kozak activity revealing distinct modes of recognition. The pre-codon triplet forms a fan-like intercalation into the 18S ribosomal RNA (rRNA), while a -3 pyrimidine destabilizes ternary complex positioning. Specificity towards the +4 purine is achieved beyond a single residue recognition by mutual conformational adaptations of eIF1A, mRNA and rRNA that involve the insertion of a reading head in which decoding residue A1825 (rRNA) stacks with the A-site codon to stabilize the fully accommodated state. Hence, instead of relying on base pairing as in bacteria, the specific recognition of the Kozak sequence on eukaryotic ribosomes is based on an induced-fit mechanism that triggers a conformational readout of the mRNA.

PubMed: 42420270
DOI: 10.1038/s41467-026-73969-2

Experimental method

ELECTRON MICROSCOPY (3.2 Å)