Related Experiment Video

Updated: Jun 13, 2026

Deciphering the Structural Effects of Activating EGFR Somatic Mutations with Molecular Dynamics Simulation
15:05

Deciphering the Structural Effects of Activating EGFR Somatic Mutations with Molecular Dynamics Simulation

Published on: May 20, 2020

Spatial structure of the transmembrane domain heterodimer of ErbB1 and ErbB2 receptor tyrosine kinases

Konstantin S Mineev1, Eduard V Bocharov, Yulia E Pustovalova

  • 1Division of Structural Biology, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry RAS, ul. Miklukho-Maklaya, 16/10, Moscow 117997, Russia.

Journal of Molecular Biology
|May 18, 2010
PubMed

Insights

The ErbB1/ErbB2 heterodimer

Area of Science:

  • Molecular Biology
  • Biophysics
  • Cancer Research

Background:

  • Growth factor receptor tyrosine kinases of the ErbB family are crucial for cellular processes and cancer.
  • ErbB receptors mediate signaling via dimerization across the plasma membrane.
  • The ErbB1/ErbB2 heterodimer is a potent inducer of cellular transformation.

Purpose of the Study:

  • To determine the spatial structure of the ErbB1/ErbB2 heterodimeric complex.
  • To elucidate the role of transmembrane (TM) domain interactions in ErbB signaling.

Main Methods:

  • Solution Nuclear Magnetic Resonance (NMR) spectroscopy.
  • Utilized lipid bicelles to mimic the cellular membrane environment.
  • Analyzed the association of ErbB1 and ErbB2 TM domains.

Main Results:

  • Determined the right-handed alpha-helical bundle structure of the ErbB1/ErbB2 TM heterodimer.
  • Identified specific motifs (GG4-like and glycine zipper) involved in TM domain association.
  • Observed multiple polar interactions and hydrogen bonding between TM segments.

Conclusions:

  • The determined heterodimer conformation supports the active state of ErbB receptors.
  • Helix-helix interactions within the TM domains significantly contribute to the high affinity of the ErbB1/ErbB2 heterodimer.
  • TM domain interactions are critical for ErbB-mediated signal transduction.

More Related Videos

Transmembrane Domain Oligomerization Propensity determined by ToxR Assay06:45

Transmembrane Domain Oligomerization Propensity determined by ToxR Assay

Published on: May 26, 2011

Production of Disulfide-stabilized Transmembrane Peptide Complexes for Structural Studies12:05

Production of Disulfide-stabilized Transmembrane Peptide Complexes for Structural Studies

Published on: March 6, 2013

Related Concept Videos

Structure of Cadherins01:25

Structure of Cadherins

The cadherins were one of the first cell adhesion molecules discovered; the term “cadherins”   is based on their calcium-dependent adhering properties. The first cadherins discovered on the epithelial, neuronal, and placental cells were named E-cadherin, P-cadherin, and N-cadherin, respectively. These classical cadherins share sequence and structural similarities. Other cadherins, including those involved in cell signaling, are grouped into non-classical cadherins. This diversity of cadherins...
Receptor Tyrosine Kinases01:26

Receptor Tyrosine Kinases

Receptor tyrosine kinases or RTKs are membrane-bound receptors that phosphorylate specific tyrosine on protein substrates. RTKs regulate cellular growth, differentiation, survival, and migration. They contain an extracellular ligand binding domain, a transmembrane domain, and a cytosolic tail with intrinsic kinase activity. Several extracellular signaling molecules activate RTKs in one or more ways and relay the signal downstream. Ligands such as platelet-derived growth factor (PDGF) or...
Insertion of Multi-pass Transmembrane Proteins in the RER01:29

Insertion of Multi-pass Transmembrane Proteins in the RER

The rough ER membrane synthesizes, assembles, and embeds transmembrane proteins in diverse topologies. These proteins function as transporters or channels and can remain in the ER membrane or are sent to the Golgi complex, lysosome, and cell membrane.
The multipass transmembrane proteins are the type IV integral membrane proteins with multiple topogenic sequences determining their spatial arrangement in the ER membrane. Nearly all multipass proteins lack a cleavable signal sequence and use...
Assembly of Signaling Complexes01:30

Assembly of Signaling Complexes

Multiprotein signaling complexes are formed in a dynamic process involving protein-protein interactions at the cytoplasmic domain of transmembrane receptors or enzymatic and non-enzymatic proteins associated with the receptor. These complexes ensure the activation and propagation of intracellular signals that regulate cell functions.
Interaction domains in cell signaling
Interaction domains recognize exposed features of their binding partners containing post-translationally modified sequences,...
Enzyme-linked Receptors01:00

Enzyme-linked Receptors

Enzyme-linked receptors are proteins that act as both receptor and enzyme, activating multiple intracellular signals. This is a large group of receptors that include the receptor tyrosine kinase (RTK) family. Many growth factors and hormones bind to and activate the RTKs.
Neurotrophin (NT) receptors are a family of RTKs, including trkA, trkB, and trkC (tropomyosin-related kinase) receptors. TrkA is specific for nerve growth factor (NGF), neurotrophin-6, and neurotrophin-7. TrkB binds...
Multi-pass Transmembrane Proteins and β-barrels01:09

Multi-pass Transmembrane Proteins and β-barrels

In multi-pass transmembrane proteins, the polypeptide chain crosses the membrane more than once. The transmembrane polypeptide chain either forms an α-helix or β-strand structure. α-Helix containing multi-pass transmembrane proteins are ubiquitous, whereas β-strand containing ones are mainly found in gram-negative bacteria, mitochondria, and chloroplasts.
α-Helix containing multi-pass transmembrane proteins
Multi-pass transmembrane proteins such as G-protein-linked receptors (GPCRs) and...