Polymorphism of the epidermal growth factor receptor extracellular ligand binding domain: the dimer interface depends on domain stabilization.

ABSTRACT: Epidermal growth factor receptors (EGFRs) and their cytoplasmic tyrosine kinases play important roles in cell proliferation and signaling. The EGFR extracellular domain (sEGFR) forms a dimer upon the binding of ligands, such as epidermal growth factor (EGF) and transforming growth factor α (TGFα). In this study, multiple molecular dynamics (MD) simulations of the 2:2 EGF·sEGFR3-512 dimer and the 2:2 TGFα·sEGFR3-512 dimer were performed in solvent and crystal environments. The simulations of systems comprising up to half a million atoms reveal part of the structural dynamics of which sEGFR dimers are capable. The solvent simulations consistently exhibited a prominent conformational relaxation from the initial crystal structures on the nanosecond time scale, leading to symmetry breaking and

SUBMITTER: Zhang Z 

PROVIDER: S-EPMC3062653 | biostudies-literature | 2011 Mar

REPOSITORIES: biostudies-literature