2K9Y

EphA2 dimeric structure in the lipidic bicelle at pH 5.0

Summary for 2K9Y

• Entry DOI: 10.2210/pdb2k9y/pdb
• Related: 2k1k 2k1l
• NMR Information: BMRB: 16005
• Descriptor: Ephrin type-A receptor 2 (2 entities in total)
• Functional Keywords: receptor tyrosine kinase, membrane protein, dimeric transmembrane domain, ephrin receptor, atp-binding, glycoprotein, kinase, membrane, nucleotide-binding, phosphoprotein, polymorphism, receptor, transferase, transmembrane, tyrosine-protein kinase
• Biological source: Homo sapiens (human)
• Cellular location: Cell membrane; Single-pass type I membrane protein: P29317
• Total number of polymer chains: 2
• Total formula weight: 8566.10

Authors

Mayzel, M.L.,Bocharov, E.V.,Volynsky, P.E.,Arseniev, A.S. (deposition date: 2008-10-27, release date: 2009-08-11, Last modification date: 2024-05-15)

Primary citation

Bocharov, E.V.,Mayzel, M.L.,Volynsky, P.E.,Mineev, K.S.,Tkach, E.N.,Ermolyuk, Y.S.,Schulga, A.A.,Efremov, R.G.,Arseniev, A.S.
Left-Handed Dimer of EphA2 Transmembrane Domain: Helix Packing Diversity among Receptor Tyrosine Kinases
Biophys.J., 98:881-889, 2010

PubMed Abstract: The Eph receptor tyrosine kinases and their membrane-bound ephrin ligands control a diverse array of cell-cell interactions in the developing and adult organisms. During signal transduction across plasma membrane, Eph receptors, like other receptor tyrosine kinases, are involved in lateral dimerization and subsequent oligomerization presumably with proper assembly of their single-span transmembrane domains. Spatial structure of dimeric transmembrane domain of EphA2 receptor embedded into lipid bicelle was obtained by solution NMR, showing a left-handed parallel packing of the transmembrane helices (535-559)(2). The helices interact through the extended heptad repeat motif L(535)X(3)G(539)X(2)A(542)X(3)V(546)X(2)L(549) assisted by intermolecular stacking interactions of aromatic rings of (FF(557))(2), whereas the characteristic tandem GG4-like motif A(536)X(3)G(540)X(3)G(544) is not used, enabling another mode of helix-helix association. Importantly, a similar motif AX(3)GX(3)G as was found is responsible for right-handed dimerization of transmembrane domain of the EphA1 receptor. These findings serve as an instructive example of the diversity of transmembrane domain formation within the same family of protein kinases and seem to favor the assumption that the so-called rotation-coupled activation mechanism may take place during the Eph receptor signaling. A possible role of membrane lipid rafts in relation to Eph transmembrane domain oligomerization and Eph signal transduction was also discussed.

PubMed: 20197042
DOI: 10.1016/j.bpj.2009.11.008

Experimental method

SOLUTION NMR