2KS1

Heterodimeric association of Transmembrane domains of ErbB1 and ErbB2 receptors Enabling Kinase Activation

Summary for 2KS1

• Entry DOI: 10.2210/pdb2ks1/pdb
• Related: 2jwa
• Descriptor: Receptor tyrosine-protein kinase erbB-2, Epidermal growth factor receptor (2 entities in total)
• Functional Keywords: erbb1, erbb2, transmembrane, heterodimer, complex, tyrosine kinase receptor, bicelles, transferase
• Biological source: Homo sapiens (human); More
• Cellular location: Cell membrane; Single-pass type I membrane protein. Isoform 2: Secreted: P04626; Isoform 1: Cell membrane; Single-pass type I membrane protein. Isoform 2: Cytoplasm. Isoform 3: Cytoplasm: P00533
• Total number of polymer chains: 2
• Total formula weight: 9468.65

Authors

Mineev, K.S.,Bocharov, E.V.,Pustovalova, Y.E.,Bocharova, O.V.,Chupin, V.V.,Arseniev, A.S. (deposition date: 2009-12-24, release date: 2010-06-09, Last modification date: 2024-05-01)

Primary citation

Mineev, K.S.,Bocharov, E.V.,Pustovalova, Y.E.,Bocharova, O.V.,Chupin, V.V.,Arseniev, A.S.
Spatial Structure of the Transmembrane Domain Heterodimer of ErbB1 and ErbB2 Receptor Tyrosine Kinases
J.Mol.Biol., 2010

PubMed Abstract: Growth factor receptor tyrosine kinases of the ErbB family play a significant role in vital cellular processes and various cancers. During signal transduction across plasma membrane, ErbB receptors are involved in lateral homodimerization and heterodimerization with proper assembly of their extracellular single-span transmembrane (TM) and cytoplasmic domains. The ErbB1/ErbB2 heterodimer appears to be the strongest and most potent inducer of cellular transformation and mitogenic signaling compared to other ErbB homodimers and heterodimers. Spatial structure of the heterodimeric complex formed by TM domains of ErbB1 and ErbB2 receptors embedded into lipid bicelles was obtained by solution NMR. The ErbB1 and ErbB2 TM domains associate in a right-handed alpha-helical bundle through their N-terminal double GG4-like motif T(648)G(649)X(2)G(652)A(653) and glycine zipper motif T(652)X(3)S(656)X(3)G(660), respectively. The described heterodimer conformation is believed to support the juxtamembrane and kinase domain configuration corresponding to the receptor active state. The capability for multiple polar interactions, along with hydrogen bonding between TM segments, correlates with the observed highest affinity of the ErbB1/ErbB2 heterodimer, implying an important contribution of the TM helix-helix interaction to signal transduction.

PubMed: 20471394
DOI: 10.1016/j.jmb.2010.05.016

Experimental method

SOLUTION NMR