Transmembrane domain of EphA1 receptor forms dimers in membrane-like environment
Autor: | Elena O. Artemenko, Alexander S. Arseniev, Alexey V. Feofanov, Natalya S. Egorova |
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Rok vydání: | 2008 |
Předmět: |
Molecular Sequence Data
Biophysics Biochemistry Receptor tyrosine kinase Transmembrane domain Protein structure Glycophorin Humans Amino Acid Sequence Receptor Micelles biology Chemistry Receptor EphA1 Erythropoietin-producing hepatocellular (Eph) receptor Cell Biology EphA1 receptor Protein Structure Tertiary Enzyme Activation Liposomes FRET biology.protein Signal transduction Peptides Tyrosine kinase Dimerization SDS-PAGE Signal Transduction |
Zdroj: | Biochimica et Biophysica Acta (BBA) - Biomembranes. 1778(10):2361-2367 |
ISSN: | 0005-2736 |
DOI: | 10.1016/j.bbamem.2008.06.003 |
Popis: | Eph receptor tyrosine kinases (RTKs) are activated by a ligand-mediated dimerization in the plasma membrane and subjected to clusterization at a high local density of receptors and their membrane-anchored ligands. Interactions between transmembrane domains (TMDs) were recognized to assist to the ligand-binding extracellular domains in the dimerization of some RTKs, whereas a functional role of Eph-receptor TMDs remains unknown. We have studied a propensity of EphA1-receptor TMDs (TMA1) to self-association in membrane-mimetic environment. Dimerization of TMA1 in SDS environment was revealed by SDS-PAGE and confirmed by FRET analysis of the fluorescently labeled peptide (Kd=7.2+/-0.4 microM at 1.5 mM SDS). TMA1 dimerization was also found in 1,2-dimyristoyl-sn-glycero-3-phosphocholine liposomes (DeltaG=-15.4+/-0.5 kJ/mol). Stability of TMA1 dimers is comparable to the reported earlier stability of TMD dimers of fibroblast growth factor receptor 3 and tenfold weaker than the stability of TMD dimers of glycophorin A possessing high propensity to dimerization. Our results suggest that EphA1-receptor TMD contribute to the dimerization-mediated receptor activation. An assumed role of the TMD interactions is the efficient signal transduction due to TMD-driving mutual orientation of kinase domains in dimers, while a relatively low force of the TMD interactions does not prevent a ligand-controlled regulation of the receptor dimerization. |
Databáze: | OpenAIRE |
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