Uncoupling of initiation factor eIF5B/IF2 GTPase and translational activities by mutations that lower ribosome affinity

Byung Sik Shin, David Maag, Antonina Roll-Mecak, M. Shamsul Arefin, Stephen K. Burley, Jon R. Lorsch, Thomas E. Dever

Research output: Contribution to journalArticle

Abstract

Translation initiation factor eIF5B/IF2 is a GTPase that promotes ribosomal subunit joining. We show that eIF5B mutations in Switch I, an element conserved in all GTP binding domains, impair GTP hydrolysis and general translation but not eIF5B subunit joining function. Intragenic suppressors of the Switch I mutation restore general translation, but not eIF5B GTPase activity. These suppressor mutations reduce the ribosome affinity of eIF5B and increase AUG skipping/leaky scanning. The uncoupling of translation and eIF5B GTPase activity suggests a regulatory rather than mechanical function for eIF5B GTP hydrolysis in translation initiation. The translational defect suggests eIF5B stabilizes Met-tRNAi Met binding and that GTP hydrolysis by eIF5B is a checkpoint monitoring 80S ribosome assembly in the final step of translation initiation.

Original languageEnglish (US)
Pages (from-to)1015-1025
Number of pages11
JournalCell
Volume111
Issue number7
DOIs
StatePublished - Dec 27 2002

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Peptide Initiation Factors
GTP Phosphohydrolases
Ribosomes
Mutation
Guanosine Triphosphate
Hydrolysis
Joining
Switches
Genetic Suppression
eukaryotic initiation factor-5B
Ribosome Subunits
Scanning
Defects
Monitoring

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

Cite this

Shin, B. S., Maag, D., Roll-Mecak, A., Arefin, M. S., Burley, S. K., Lorsch, J. R., & Dever, T. E. (2002). Uncoupling of initiation factor eIF5B/IF2 GTPase and translational activities by mutations that lower ribosome affinity. Cell, 111(7), 1015-1025. https://doi.org/10.1016/S0092-8674(02)01171-6

Uncoupling of initiation factor eIF5B/IF2 GTPase and translational activities by mutations that lower ribosome affinity. / Shin, Byung Sik; Maag, David; Roll-Mecak, Antonina; Arefin, M. Shamsul; Burley, Stephen K.; Lorsch, Jon R.; Dever, Thomas E.

In: Cell, Vol. 111, No. 7, 27.12.2002, p. 1015-1025.

Research output: Contribution to journalArticle

Shin, BS, Maag, D, Roll-Mecak, A, Arefin, MS, Burley, SK, Lorsch, JR & Dever, TE 2002, 'Uncoupling of initiation factor eIF5B/IF2 GTPase and translational activities by mutations that lower ribosome affinity', Cell, vol. 111, no. 7, pp. 1015-1025. https://doi.org/10.1016/S0092-8674(02)01171-6
Shin, Byung Sik ; Maag, David ; Roll-Mecak, Antonina ; Arefin, M. Shamsul ; Burley, Stephen K. ; Lorsch, Jon R. ; Dever, Thomas E. / Uncoupling of initiation factor eIF5B/IF2 GTPase and translational activities by mutations that lower ribosome affinity. In: Cell. 2002 ; Vol. 111, No. 7. pp. 1015-1025.
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