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. Extendin
g those results, we have solved the structure of the carboxyl-terminal doma
in of elF4A with data to 1.75 Angstrom resolution; it has a parallel LY-P t
opology that superimposes, with minor variations, on the structures and con
served motifs of the equivalent domain in other, distantly related helicase
s. Using data to 2.8 Angstrom resolution and molecular replacement with the
refined model of the carboxyl-terminal domain, we have completed the struc
ture of full-length elF4A; it is a "dumbbell" structure consisting of two c
ompact 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 conser
ved in the DEA(D/H)-box RNA helicase family but is absent from many other h
elicases, also binds RNA; and (iii) motifs V and VI "link" the carboxyl-ter
minal domain to the amino-terminal domain through interactions with ATP and
the DEA(D/H) motif, providing a mechanism for coupling ATP binding and hyd
rolysis with conformational changes that modulate RNA binding.