Looking at Accountability 40 Years after Darling

An examination of the ramifications of the Darling decision

Book Reviews

TRIAL BY JURY. By Samuel W. McCart. CLINICAL INVESTIGATION IN MEDICINE: Legal, Ethical and Moral Aspects. Edited by Irving Ladimer and Roger W. Newman. RELIGION AND THE CONSTITUTION. By Paul G. Kauper

Looking at Accountability 40 Years after Darling

An examination of the ramifications of the Darling decision

Folding transitions during assembly of the eukaryotic mRNA cap-binding complex.

The cap-binding protein eIF4E is the first in a chain of translation initiation factors that recruit 40S ribosomal subunits to the 5' end of eukaryotic mRNA. During cap-dependent translation, this protein binds to the 5'-terminal m(7)Gppp cap of the mRNA, as well as to the adaptor protein eIF4G. The latter then interacts with small ribosomal subunit-bound proteins, thereby promoting the mRNA recruitment process. Here, we show apo-eIF4E to be a protein that contains extensive unstructured regions, which are induced to fold upon recognition of the cap structure. Binding of eIF4G to apo-eIF4E likewise induces folding of the protein into a state that is similar to, but not identical with, that of cap-bound eIF4E. At the same time, binding of each of the binding partners of eIF4E modulates the kinetics with which it interacts with the other partner. We present structural, kinetic and mutagenesis data that allow us to deduce some of the detailed folding transitions that take place during the eIF4E interactions