FGFR2 Protein

The FGFR2 protein has a vital role as a receptor at the surface of cells that express fibroblast growth factors (FGFs). It activates many important signals within the cell that mediate cell growth, differentiation, and death, especially during fetal development.

The FGFR2 protein has 3 domains: one outside the cell, one across the border of the cell, and one inside. The region outside the cell contains 3 receptors for FGFs to bind, known as Ig I, Ig II, and Ig III, as illustrated in Figure 4. [1,2,3,4]

Figure 4. FGFR2 protein structure and location. For cell signalling to occur, the Ig III regions of two different FGFR2 proteins bind to FGF, making the protein active. Created in Biorender.com

Taking a closer look at region outside the cell, we can explore the different structures that make up this important section of the protein.

primary

At the most basic level, the protein is made up of chains of 'amino acids'. These are the building blocks of a protein, and there are 20 different ones, with varying properties: they can be acidic, water-loving, water-hating etc.

Every three letters in our DNA encodes for a type of amino acid, and just one letter change can result in a alteration in the primary structure, as is the case in Crouzon Syndrome.


Secondary

The interaction of different amino acids due to their various properties lead to the secondary structure formation of a protein.

FGFR2 has:

  • 2 beta-sheets

  • 3 alpha helices (spirals)

  • 2 alpha turns (shorter spirals)

tertiary

Secondary structures interact with each other to form the three dimensional protein. Notably, cysteine (cys) is the only amino acid that has the ability to form a bridge between itself and another cysteine through its sulfide components, stabilising the structure around the beta sheet region. This is highlighted in the video below.

MAT video.mp4

Figure 5. A narrated video demonstrating the structure of the FGF-FGFR2-heparin active complex. Created with data from https://www.rcsb.org/structure/1E0O using The PyMOL Molecular Graphics System, Version 2.0 Schrödinger, LLC.

References

  1. UniProt [Internet]. Uniprot.org. 2022 [cited 2022 Oct 21]. Available from: https://www.uniprot.org/uniprotkb/P21802/entry#ptm_processing

  2. 1E0O: Crystal structure of a ternary FGF1-FGFR2-heparin complex [Internet]. Nih.gov. 2014 [cited 2022 Oct 21]. Available from: https://www.ncbi.nlm.nih.gov/Structure/mmdb/mmdbsrv.cgi?dps=0&uid=1E0O

  3. Dai S, Zhou Z, Chen Z, Xu G, Chen Y. Fibroblast Growth Factor Receptors (FGFRs): Structures and Small Molecule Inhibitors. Cells. [Internet] 2019 [cited 2022 Oct 22];8(6):614. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6627960/

  4. Pellegrini L, Burke D, von Delft F. Crystal structure of fibroblast growth factor receptor ectodomain bound to ligand and heparin. Nature. [Internet] 2000 [cited 2022 Oct 22] 407;1029–1034; Available from: https://www.nature.com/articles/35039551