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6olf

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Revision as of 10:17, 23 October 2024 by OCA (Talk | contribs)

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Human ribosome nascent chain complex (CDH1-RNC) stalled by a drug-like molecule with AA and PE tRNAs

6olf, resolution 3.90Å

Structural highlights

6olf is a 10 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	Electron Microscopy, Resolution 3.9Å
Ligands:
Experimental data:	Check to display Experimental Data
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

RS5_HUMAN

Publication Abstract from PubMed

The drug-like molecule PF-06446846 (PF846) binds the human ribosome and selectively blocks the translation of a small number of proteins by an unknown mechanism. In structures of PF846-stalled human ribosome nascent chain complexes, PF846 binds in the ribosome exit tunnel in a eukaryotic-specific pocket formed by 28S ribosomal RNA, and alters the path of the nascent polypeptide chain. PF846 arrests the translating ribosome in the rotated state of translocation, in which the peptidyl-transfer RNA 3'-CCA end is improperly docked in the peptidyl transferase center. Selections of messenger RNAs from mRNA libraries using translation extracts reveal that PF846 can stall translation elongation, arrest termination or even enhance translation, depending on nascent chain sequence context. These results illuminate how a small molecule selectively targets translation by the human ribosome, and provides a foundation for developing small molecules that modulate the production of proteins of therapeutic interest.

Structural basis for selective stalling of human ribosome nascent chain complexes by a drug-like molecule.,Li W, Ward FR, McClure KF, Chang ST, Montabana E, Liras S, Dullea RG, Cate JHD Nat Struct Mol Biol. 2019 Jun;26(6):501-509. doi: 10.1038/s41594-019-0236-8. Epub, 2019 Jun 3. PMID:31160784^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Li W, Ward FR, McClure KF, Chang ST, Montabana E, Liras S, Dullea RG, Cate JHD. Structural basis for selective stalling of human ribosome nascent chain complexes by a drug-like molecule. Nat Struct Mol Biol. 2019 Jun;26(6):501-509. doi: 10.1038/s41594-019-0236-8. Epub, 2019 Jun 3. PMID:31160784 doi:http://dx.doi.org/10.1038/s41594-019-0236-8