PDEδ Binding to Ras Isoforms Provides a Route to Proper Membrane Localization.

ABSTRACT: To signal, Ras isoforms must be enriched at the plasma membrane (PM). It was suggested that phosphodiesterase-δ (PDEδ) can bind and shuttle some farnesylated Ras isoforms to the PM, but not all. Among these, interest focused on K-Ras4B, the most abundant oncogenic Ras isoform. To study PDEδ/Ras interactions, we modeled and simulated the PDEδ/K-Ras4B complex. We obtained structures, which were similar to two subsequently determined crystal structures. We next modeled and simulated complexes of PDEδ with the farnesylated hypervariable regions of K-Ras4A and N-Ras. Earlier data suggested that PDEδ extracts K-Ras4B and N-Ras from the PM, but surprisingly not K-Ras4A. Earlier analysis of the crystal structures advanced that the presence of large/charged residues adjacent to the farnesylated sit

SUBMITTER: Muratcioglu S 

PROVIDER: S-EPMC7891760 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature