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Putting together structures of epidermal growth factor receptors

Larry H Bernstein, MD, FCAP, Writer and Curator

https://pharmaceuticalintelligence.com/2015/04/07/larryhbern/Puttin _together_structures_of_epidermal_growth_factor_receptors

7.3.5 Putting together structures of epidermal growth factor receptors

Bessman NJ, Freed DM, Lemmon MA
Curr Opin Struct Biol. 2014 Dec; 29:95-101
http://dx.doi.org:/10.1016/j.sbi.2014.10.002

Highlights

• Several studies suggest flexible linkage between extracellular and intracellular regions. • Others imply more rigid connections, required for allosteric regulation of dimers. • Interactions with membrane lipids play important roles in EGFR regulation. • Cellular studies suggest half-of-the-sites negative cooperativity for human EGFR.

Numerous crystal structures have been reported for the isolated extracellular region and tyrosine kinase domain of the epidermal growth factor receptor (EGFR) and its relatives, in different states of activation and bound to a variety of inhibitors used in cancer therapy. The next challenge is to put these structures together accurately in functional models of the intact receptor in its membrane environment. The intact EGFR has been studied using electron microscopy, chemical biology methods, biochemically, and computationally. The distinct approaches yield different impressions about the structural modes of communication between extracellular and intracellular regions. They highlight possible differences between ligands, and also underline the need to understand how the receptor interacts with the membrane itself.

http://ars.els-cdn.com/content/image/1-s2.0-S0959440X14001304-gr1.sml

http://ars.els-cdn.com/content/image/1-s2.0-S0959440X14001304-gr2.sml