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

The eukaryotic translation initiation factor 4A (elF4A) 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 elF4A. Extending those results, we have solved the structure of the carboxyl-terminal domain of elF4A with data to 1.75 Angstrom resolution; it has a parallel LY-P 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 Angstrom resolution and molecular replacement with the refined model of the carboxyl-terminal domain, we have completed the structure of full-length elF4A; 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 elF4A 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.