The structural biology of growth factor receptor activation

Related Experiment Video

Updated: Sep 26, 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

Nicholas J Harmer1, Dima Chirgadze, Kyung Hyun Kim

  • 1Department of Biochemistry, University of Cambridge, 80 Tennis Court Road, Cambridge CB2 1GA, UK.

Biophysical Chemistry
|March 21, 2003
PubMed

Insights

Growth factors, essential for cell responses, bind receptors via their globular structure. Diverse binding mechanisms, including monomeric and dimeric forms, facilitate receptor activation and downstream signaling pathways.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Growth factors orchestrate crucial cellular processes like growth, differentiation, migration, and survival.
  • Many growth factors utilize receptor tyrosine kinases (RTKs) for signal transduction, involving receptor dimerization and autophosphorylation.
  • Understanding the precise mechanisms of growth factor-receptor interaction is key to deciphering cellular signaling.

Purpose of the Study:

  • To investigate the role of growth factor architecture in receptor binding.
  • To elucidate the diverse molecular mechanisms by which different growth factors (NGF, HGF/SF, FGF, insulin, IGF) interact with their respective receptors.
  • To propose a general model for growth factor-receptor complex formation.

Main Methods:

  • Comparative analysis of growth factor structures and their known receptor interactions.
  • Review of existing literature on signaling cascades initiated by specific growth factors.
  • Structural and functional characterization of growth factor-receptor complexes.

Main Results:

  • The globular architecture of growth factors is critical for effective receptor binding.
  • Nerve growth factor (NGF) forms a symmetrical hetero-hexameric complex (7SNGF) that dimerizes its receptor.
  • Hepatocyte growth factor/scatter factor (HGF/SF) and fibroblast growth factor (FGF) likely bind receptors as dimers, often stabilized by heparan sulfate.
  • Insulin and insulin-like growth factor (IGF) bind as monomers to pre-formed receptor dimers.

Conclusions:

  • Growth factor-receptor binding involves diverse molecular strategies, including monomeric and dimeric interactions.
  • Cooperative interactions between growth factors, receptor domains, and accessory molecules like heparan sulfate enhance binding specificity and complex formation.
  • These findings provide a generalized framework for understanding signal transduction initiation by growth factors.

More Related Videos

Studying the Stoichiometry of Epidermal Growth Factor Receptor in Intact Cells using Correlative Microscopy09:16

Studying the Stoichiometry of Epidermal Growth Factor Receptor in Intact Cells using Correlative Microscopy

Published on: September 11, 2015

Related Concept Videos

G Protein-coupled Receptors01:15

G Protein-coupled Receptors

G Protein-Coupled Receptors or GPCRs are membrane-bound receptors that transiently associate with heterotrimeric G proteins and induce an appropriate response to sensory stimuli such as light, odors, hormones, cytokines, or neurotransmitters.
GPCRs are also called heptahelical, 7TM, or serpentine receptors, and consist of seven (H1-H7) transmembrane alpha-helices that span the bilayer to form a cylindrical core. The transmembrane helices are connected by three extracellular loops and three...
G Protein-coupled Receptors01:15

G Protein-coupled Receptors

G Protein-Coupled Receptors or GPCRs are membrane-bound receptors that transiently associate with heterotrimeric G proteins and induce an appropriate response to sensory stimuli such as light, odors, hormones, cytokines, or neurotransmitters.
GPCRs are also called heptahelical, 7TM, or serpentine receptors, and consist of seven (H1-H7) transmembrane alpha-helices that span the bilayer to form a cylindrical core. The transmembrane helices are connected by three extracellular loops and three...
Mitogens and the Cell Cycle02:38

Mitogens and the Cell Cycle

Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...
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,...
Amplifying Signals via Enzymatic Cascade01:22

Amplifying Signals via Enzymatic Cascade

When a ligand binds to a cell-surface receptor, the receptor's intracellular domain changes shape, which may either activate its enzyme function or allow its binding to other molecules. The initial signal is amplified by most signal transduction pathways. This means that a single ligand molecule can activate multiple molecules of a downstream target. Proteins that relay a signal are most commonly phosphorylated at one or more sites, activating or inactivating the protein. Kinases catalyze the...
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...