Unknown

Dataset Information

0

Mextli proteins use both canonical bipartite and novel tripartite binding modes to form eIF4E complexes that display differential sensitivity to 4E-BP regulation.


ABSTRACT: The eIF4E-binding proteins (4E-BPs) are a diverse class of translation regulators that share a canonical eIF4E-binding motif (4E-BM) with eIF4G. Consequently, they compete with eIF4G for binding to eIF4E, thereby inhibiting translation initiation. Mextli (Mxt) is an unusual 4E-BP that promotes translation by also interacting with eIF3. Here we present the crystal structures of the eIF4E-binding regions of the Drosophila melanogaster (Dm) and Caenorhabditis elegans (Ce) Mxt proteins in complex with eIF4E in the cap-bound and cap-free states. The structures reveal unexpected evolutionary plasticity in the eIF4E-binding mode, with a classical bipartite interface for Ce Mxt and a novel tripartite interface for Dm Mxt. Both interfaces comprise a canonical helix and a noncanonical helix that engage the dorsal and lateral surfaces of eIF4E, respectively. Remarkably, Dm Mxt contains a C-terminal auxiliary helix that lies anti-parallel to the canonical helix on the eIF4E dorsal surface. In contrast to the eIF4G and Ce Mxt complexes, the Dm eIF4E-Mxt complexes are resistant to competition by bipartite 4E-BPs, suggesting that Dm Mxt can bind eIF4E when eIF4G binding is inhibited. Our results uncovered unexpected diversity in the binding modes of 4E-BPs, resulting in eIF4E complexes that display differential sensitivity to 4E-BP regulation.

SUBMITTER: Peter D 

PROVIDER: S-EPMC4573856 | biostudies-literature | 2015 Sep

REPOSITORIES: biostudies-literature

altmetric image

Publications

Mextli proteins use both canonical bipartite and novel tripartite binding modes to form eIF4E complexes that display differential sensitivity to 4E-BP regulation.

Peter Daniel D   Weber Ramona R   Köne Carolin C   Chung Min-Yi MY   Ebertsch Linda L   Truffault Vincent V   Weichenrieder Oliver O   Igreja Cátia C   Izaurralde Elisa E  

Genes & development 20150820 17


The eIF4E-binding proteins (4E-BPs) are a diverse class of translation regulators that share a canonical eIF4E-binding motif (4E-BM) with eIF4G. Consequently, they compete with eIF4G for binding to eIF4E, thereby inhibiting translation initiation. Mextli (Mxt) is an unusual 4E-BP that promotes translation by also interacting with eIF3. Here we present the crystal structures of the eIF4E-binding regions of the Drosophila melanogaster (Dm) and Caenorhabditis elegans (Ce) Mxt proteins in complex wi  ...[more]

Similar Datasets

| S-EPMC4718053 | biostudies-other
| S-EPMC4431810 | biostudies-literature
| S-EPMC9119464 | biostudies-literature
| S-EPMC6324996 | biostudies-literature
| S-EPMC4924540 | biostudies-literature
| S-EPMC4164784 | biostudies-literature
| S-EPMC3082885 | biostudies-literature
| S-EPMC6124814 | biostudies-literature
| S-EPMC5557982 | biostudies-literature
| S-EPMC309682 | biostudies-other