Leave a Message
My Cart ()
Inquiry Basket
Contact Us

Structural Research of Receptor Tyrosine Kinase (RTK) Family

Inquiry

Receptor tyrosine kinases (RTK) are single transmembrane receptors that catalyze the transfer of γ-phosphate from ATP to tyrosine residues in protein substrates. Research has shown that RTK dimerization and phosphorylation of specific tyrosine residues in the cytoplasmic fraction are promoted by ligand binding. This enhances RTK catalytic activity and provides docking sites for downstream signaling proteins. RTK plays a critical role in embryogenesis, normal physiology, and a wide range of diseases and has become an essential target for cancer drugs. Therefore, cutting-edge technologies such as X-ray crystallography and cryo-electron microscopy are needed to deepen the understanding of the molecular mechanism of RTK.

Advances in RTK research technology

Further progress in understanding RTK activation will require an understanding of the overall ligand-specific dimerization microstates of each RTK. And while crystal structure-based, biophysical methods such as small-angle X-ray scattering (SAXS) and hydrogen provide critical insights into protein static picture-deuterium exchange mass spectrometry (HXD) to reveal changes in RTK conformation throughout the activation process, it is increasingly possible to apply nuclear magnetic resonance (NMR) to research RTK structures in solution.

Structural analysis of RTK

Using negative staining electron microscopy (NS-EM) and cryo-electron microscopy (cryo-EM), it is possible to observe the conformation of full-length RTK proteins deposited on EM grids. In contrast to non-receptor TK, RTK has an extracellular region at the N-terminal end of the protein containing an extracellular domain for recognition of extracellular signaling molecules, an α-helix that spans the plasma membrane, and a structural domain of the C-terminal tyrosine kinase. RTK undergoes conformational changes, mainly involving dimerization, which leads to activation of the kinase and transmission of the signal into the cell.

Ligand-bound dimeric RTK structures.  Figure 1. Ligand-bound dimeric RTK structures. (Rygiel KA, Elkins JM, 2023)

Protein Organism Method Resolution PDB Entry ID
The kinase domain of RTKC8 Monosiga brevicollis X-ray diffraction 1.95 Å 8E4T
FGFR1 in complex with ponatinib. Homo sapiens X-ray diffraction 2.12 Å 4V04
Ephrin B4 (EphB4) receptor protein kinase with Dasatinib Homo sapiens Cryo-EM single particle analysis 1.157 Å 6FNM
Insulin receptor-related receptor's transmembrane domain Homo sapiens SOLUTION NMR / 7PL4
EphB4 kinase domain inhibitor complex Homo sapiens X-ray diffraction 2.11 Å 2YN8
Ephrin B4 (EphB4) Receptor Protein Kinase Homo sapiens X-ray diffraction 1.269 Å 6FNL
EphB4 kinase domain with an oxindole inhibitor Homo sapiens X-ray diffraction 2.33 Å 4AW5
Insulin receptor-related receptor (IRR) in apo-state captured at pH 7 Homo sapiens Cryo-EM single particle analysis 3.5 Å 7TYK
Insulin receptor-related receptor (IRR) in apo-state captured at pH 7 Homo sapiens Cryo-EM single particle analysis 3.3 Å 7TYJ
Insulin receptor-related receptor (IRR) in active-state captured at pH 9 Homo sapiens Cryo-EM single particle analysis 3.4 Å 7TYM
EphB4 in complex with staurosporine Homo sapiens X-ray diffraction 2.5 Å 3ZEW
FGFR1 in complex with AZD4547. Homo sapiens X-ray diffraction 2.57 Å 4V05
LTK: ALKAL1 complex stabilized by a Nanobody Homo sapiens X-ray diffraction 1.59 Å 7NX0
dimeric transmembrane domain of the receptor tyrosine kinase EphA1 in lipid bicelles at pH 4.3 Homo sapiens SOLUTION NMR / 2K1K
dimeric transmembrane domain of the receptor tyrosine kinase EphA1 in lipid bicelles at pH 6.3 Homo sapiens SOLUTION NMR / 2K1L
Sam domain from the receptor tyrosine kinase EphB2 Gallus gallus SOLUTION NMR / 1SGG
Extracellular WNT-binding module Drosophila melanogaster X-ray diffraction 1.75 Å 7ME4
Ephrin B4 (EphB4) Receptor Protein Kinase with NVP-BHG712 Homo sapiens X-ray diffraction 1.468 Å 6FNI
TG domain of LTK Homo sapiens X-ray diffraction 1.3 Å 7NX1
SAM Domain of Human Ephrin Type-B Receptor 4 Homo sapiens X-ray diffraction 2.1 Å 2QKQ
SAM Domain of Human Ephrin Type-A Receptor 1 (EphA1) Homo sapiens X-ray diffraction 2 Å 3HIL

Table 1. Structural research of receptor tyrosine kinase (RTK) family.

Creative Biostructure is a leading provider of biomolecular structural research, offering personalized solutions and flexible collaboration opportunities to meet clients' specific requirements. Whether it is basic structural research or functional analysis of the receptor tyrosine kinase (RTK) family, we provide accurate and reliable results.

With cutting-edge technologies including cryo-electron microscopy (cryo-EM), NMR spectroscopy, and X-ray crystallography, we can provide high-resolution structural analysis services. Our team consists of experienced scientists and researchers solving intricate biological problems. If you require structural research in biomolecules, contact us and our service will help you closer to achieving your scientific goals.

References

  1. Dyla M, et al. Structure and Mechanism of P-Type ATPase Ion Pumps. Annu Rev Biochem. 2020。89:583-603.
  2. Bublitz M, et al. Structural studies of P-type ATPase-ligand complexes using an X-ray free-electron laser. IUCrJ. 2015.2(Pt 4):409-420.
  3. Dyla M, et al. Structural dynamics of P-type ATPase ion pumps. Biochem Soc Trans. 2019。47(5):1247-1257.
OUR VALUED PARTNERSHIPS
mit harvard stanford nih abbvie novartis amgen gsk regeneron sanofi

Online Inquiry

This site is protected by reCAPTCHA and the Google Privacy Policy and Terms of Service apply.

Inquiry
back to top
Advertisement Learn More