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-Structure paper
Title | HCV IRES manipulates the ribosome to promote the switch from translation initiation to elongation. |
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Journal, issue, pages | Nat Struct Mol Biol, Vol. 20, Issue 2, Page 150-158, Year 2013 |
Publish date | Dec 23, 2012 |
Authors | Megan E Filbin / Breanna S Vollmar / Dan Shi / Tamir Gonen / Jeffrey S Kieft / |
PubMed Abstract | The internal ribosome entry site (IRES) of the hepatitis C virus (HCV) drives noncanonical initiation of protein synthesis necessary for viral replication. Functional studies of the HCV IRES have ...The internal ribosome entry site (IRES) of the hepatitis C virus (HCV) drives noncanonical initiation of protein synthesis necessary for viral replication. Functional studies of the HCV IRES have focused on 80S ribosome formation but have not explored its role after the 80S ribosome is poised at the start codon. Here, we report that mutations of an IRES domain that docks in the 40S subunit's decoding groove cause only a local perturbation in IRES structure and result in conformational changes in the IRES-rabbit 40S subunit complex. Functionally, the mutations decrease IRES activity by inhibiting the first ribosomal translocation event, and modeling results suggest that this effect occurs through an interaction with a single ribosomal protein. The ability of the HCV IRES to manipulate the ribosome provides insight into how the ribosome's structure and function can be altered by bound RNAs, including those derived from cellular invaders. |
External links | Nat Struct Mol Biol / PubMed:23262488 / PubMed Central |
Methods | EM (single particle) |
Resolution | 17.5 Å |
Structure data | EMDB-5527: |
Source |
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