Dynamical Rearrangement of Human Epidermal Growth Factor Receptor 2 upon Antibody Binding: Effects on the Dimerization.

ABSTRACT: Human epidermal growth factor 2 (HER2) is a ligand-free tyrosine kinase receptor of the HER family that is overexpressed in some of the most aggressive tumours. Although it is known that HER2 dimerization involves a specific region of its extracellular domain, the so-called "dimerization arm", the mechanism of dimerization inhibition remains uncertain. However, uncovering how antibody interactions lead to inhibition of HER2 dimerization is of key importance in understanding its role in tumour progression and therapy. Herein, we employed several computational modelling techniques for a molecular-level understanding of the interactions between HER and specific anti-HER2 antibodies, namely an antigen-binding (Fab) fragment (F0178) and a single-chain variable fragment from Trastuzumab (scFv).

SUBMITTER: Magalhaes PR 

PROVIDER: S-EPMC6920943 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature