Targeting trimeric transmembrane domain 5 of oncogenic latent membrane protein 1 using a computationally designed peptide.

ABSTRACT: Protein-protein interactions are involved in diverse biological processes. These interactions are therefore vital targets for drug development. However, the design of peptide modulators targeting membrane-based protein-protein interactions is a challenging goal owing to the lack of experimentally-determined structures and efficient protocols to probe their functions. Here we employed rational peptide design and molecular dynamics simulations to design a membrane-insertable peptide that disrupts the strong trimeric self-association of the fifth transmembrane domain (TMD5) of the oncogenic Epstein-Barr virus (EBV) latent membrane protein-1 (LMP-1). The designed anti-TMD5 peptide formed 1 : 2 heterotrimers with TMD5 in micelles and inhibited TMD5 oligomerization in bacterial membranes. Moreov

SUBMITTER: Wang Y 

PROVIDER: S-EPMC6761861 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature