Crystal structure of yeast initiation factor 4A, a DEAD-box RNA helicase

Proc Natl Acad Sci U S A. 2000 Nov 21;97(24):13080-5. doi: 10.1073/pnas.97.24.13080.

Abstract

The eukaryotic translation initiation factor 4A (eIF4A) is a member of the DEA(D/H)-box RNA helicase family, a diverse group of proteins that couples an ATPase activity to RNA binding and unwinding. Previous work has provided the structure of the amino-terminal, ATP-binding domain of eIF4A. Extending those results, we have solved the structure of the carboxyl-terminal domain of eIF4A with data to 1.75 A resolution; it has a parallel alpha-beta topology that superimposes, with minor variations, on the structures and conserved motifs of the equivalent domain in other, distantly related helicases. Using data to 2.8 A resolution and molecular replacement with the refined model of the carboxyl-terminal domain, we have completed the structure of full-length eIF4A; it is a "dumbbell" structure consisting of two compact domains connected by an extended linker. By using the structures of other helicases as a template, compact structures can be modeled for eIF4A that suggest (i) helicase motif IV binds RNA; (ii) Arg-298, which is conserved in the DEA(D/H)-box RNA helicase family but is absent from many other helicases, also binds RNA; and (iii) motifs V and VI "link" the carboxyl-terminal domain to the amino-terminal domain through interactions with ATP and the DEA(D/H) motif, providing a mechanism for coupling ATP binding and hydrolysis with conformational changes that modulate RNA binding.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Crystallography, X-Ray
  • Eukaryotic Initiation Factor-4A
  • Models, Molecular
  • Peptide Initiation Factors / chemistry*
  • Protein Conformation
  • Protein Structure, Secondary
  • RNA Helicases / chemistry*
  • Saccharomyces cerevisiae / enzymology

Substances

  • Peptide Initiation Factors
  • Eukaryotic Initiation Factor-4A
  • RNA Helicases

Associated data

  • PDB/1FUK
  • PDB/1FUU