title: Energetics of ErbB1 transmembrane domain dimerization in lipid bilayers.
abstract: One of the most extensively studied receptor tyrosine kinases is EGFR/ErbB1. Although our knowledge of the role of the extracellular domains and ligands in ErbB1 activation has increased dramatically based on solved domain structures, the exact mechanism of signal transduction across the membrane remains unknown. The transmembrane domains are expected to play an important role in the dimerization process, but the contribution of ErbB1 TM domain to dimer stability is not known, with published results contradicting one another. We address this controversy by showing that ErbB1 TM domain dimerizes in lipid bilayers and by calculating its contribution to stability as -2.5 kcal/mol. The stability calculations use two different methods based on Förster resonance energy transfer, which give the same result. The ErbB1 TM domain contribution to stability exceeds the change in receptor tyrosine kinases dimerization propensities that can convert normal signaling processes into pathogenic processes, and is thus likely important for biological function.
authors.affiliation: Department of Materials Science and Engineering Johns Hopkins University, Baltimore, MD 21218, USA.
authors.forename: Lirong
authors.initials: L
authors.lastname: Chen
authors.forename: Mikhail
authors.initials: M
authors.lastname: Merzlyakov
authors.forename: Tomer
authors.initials: T
authors.lastname: Cohen
authors.forename: Yechiel
authors.initials: Y
authors.lastname: Shai
authors.forename: Kalina
authors.initials: K
authors.lastname: Hristova
mesh_terms: D000465:Algorithms; D002942:Circular Dichroism; D003902:Detergents / Q000737:chemistry; D004591:Electrophoresis, Polyacrylamide Gel; D066246:ErbB Receptors / Q000737:chemistry*; D019793:Fluorescein; D008051:Lipid Bilayers / Q000737:chemistry*; D010713:Phosphatidylcholines / Q000737:chemistry; D055503:Protein Multimerization; D055550:Protein Stability; D017433:Protein Structure, Secondary; D012235:Rhodamines; D015398:Signal Transduction; D013050:Spectrometry, Fluorescence
chemical_list: D003902:Detergents; D008051:Lipid Bilayers; D010713:Phosphatidylcholines; D012235:Rhodamines; C015153:1,2-dilauroylphosphatidylcholine; D066246:ErbB Receptors; C028694:1-palmitoyl-2-oleoylphosphatidylcholine; D019793:Fluorescein