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Home List of Titles Conformational dynamics in a truncated epidermal growth factor receptor ectodomain
Please use this identifier to cite or link to this item: http://hdl.handle.net/1959.3/195677
- Conformational dynamics in a truncated epidermal growth factor receptor ectodomain
- Kozer, Noga; Rothacker, Julie; Burgess, Antony W.; Nice, Edouard C.; Clayton, Andrew H. A.
- Structural studies have revealed two forms of the monomeric epidermal growth factor receptor (EGFR) ectodomain: a compact (tethered) form stabilized by interdomain interactions and an extended (untethered) form in the presence of ligand. An important question is whether the ligand induces a conformational transition from a tethered to untethered form or whether there is a preexisting conformational equilibrium between tethered and untethered states. To distinguish between these two possibilities, we investigated a truncated receptor, EGFR501 (spanning residues 1-501), that contains the minimal elements required for high-affinity ligand binding in solution. Conformational transitions and dynamics were inferred by means of fluorescence from five internal tryptophan residues that are located within or close to the ligand-binding domains of EGFR501. A preexisting conformational equilibrium between tethered and untethered states in EGFR501 was deduced from (1) the nonlinear Arrhenius temperature dependence of fluorescence and (2) fluorescence polarization showing independently mobile domains. In contrast, the ligand EGFR501 complex revealed a linear Arrhenius temperature dependence of fluorescence and increased fluorescence polarization due to a lack of significant interdomain motions. The data suggest that the role of the ligand is to trap the EGFR501 in the untethered state that is transiently formed in solution through a preexisting conformational equilibrium.
- Publication type
- Journal article
- Research centre
- Swinburne University of Technology. Faculty of Engineering and Industrial Sciences. Centre for Micro-Photonics
- Biochemistry, Vol. 50, no. 23 (Jun 2011), pp. 5130-5139
- Publication year
- FOR Code(s)
- 0601 Biochemistry and Cell Biology; 1101 Medical Biochemistry and Metabolomics
- Cell surface; Conformational transition; Ectodomains; EGFR501; Epidermal growth factor receptor; Fluorescence; Ligand binding; Truncated receptor
- American Chemical Society
- Publisher URL
- Copyright © 2011 American Chemical Society.
- Research Projects
- Additional information
- Supported by an R. D. Wright Biomedical Career Development Award from the Australian National Health and Medical Research Council (NHMRC).
- Peer reviewed