Structural arrangement of the active back-to-back dimer in N-glycosylated ErbB receptors is regulated by heterodimerization
Journal: Molecular Biology Research Communications (Vol.12, No. 3)Publication Date: 2023.09.01
Authors : Romina Mashayekh-Poul; Maryam Azimzadeh-Irani; Seyedeh Zeinab Masoomi-Nomandan;
Page : 95-107
Keywords : ErbB receptors; Dimerization; Back-to-back dimer; Molecular modeling;
Abstract
The human epidermal growth factor receptor (EGFR/ErbB) family consists of four members (ErbB1-4) and belongs to the superfamily of receptor tyrosine kinases (RTKs). The ErbB family members participate in multiple cellular pathways and are the key players in several cancers (brain, breast, lung etc.). Activation of these family members depends on their extracellular domains forming back-to-back hetero/homo dimers. Moreover, dimers are glycosylated, which is a crucial post-translational modification that affects the conformation and function of the protein. Here, molecular modeling and molecular docking are used to comprehensively investigate the dimerization mechanism in glycosylated back-to-back active dimer formation in the entire ErbB receptors for the first time. Results showed that 21 out of 37 clusters of active back-to-back dimers formed by all family members are through heterodimerization. Including; ErbB1-ErbB3/ErbB4, ErbB2-ErbB3/ErbB4 and ErbB3-ErbB4. Ranking ErbB2-ErbB3 as the most stabilized back-to-back dimeric construct. While glycan arrangements favor both homo/hetero dimerization at the dimeric interfaces, it promotes heterodimerization by stabilizing and packing the ligand binding sites of EGFR and ErbB2 respectively. These findings pave the path to future heterodimeric interface/glycan targeting rational anti-cancer drug designs for ErbB receptors.
Other Latest Articles
- Detection of Hepatozoon spp. in dogs in Shiraz, southern Iran and its effects on the hematological alterations
- The effect of Annexin A5 overexpression on invasiveness and expression of the genes involved in epithelial-mesenchymal transition of HCT 116 cell line
- Gold Bio-recovery from Electronic Waste Using Aspergillus niger: A Case Study
- Efficacy of Gandusha on Oral Health: A Potential Natural Ayurvedic Remedy for Gutkha Chewers
- Characterization of Extracellular Polymeric Substances (EPS) Producing Bacteria Isolated from Biofilms Developed on Different Support Materials in Attached Growth Batch Reactors
Last modified: 2023-09-05 15:40:06