Skip to main content
. Author manuscript; available in PMC: 2023 Apr 1.
Published in final edited form as: Cytokine Growth Factor Rev. 2021 Nov 17;64:71–83. doi: 10.1016/j.cytogfr.2021.11.002

Figure 1: Different domains and structural organization of GDF15:

Figure 1:

(A) The GDF15 gene is located on chromosome 19p13.11 and contains two exons and one intronic region. The primary immature linear sequence known as pre-pro-peptide GDF15 consists of a signal peptide (amino acid residues 1-29), following by a pro-peptide sequence (amino acids 30-194), and GDF15. The cleavage of the pre-pro-peptide liberates mature GDF15, which exists as a homodimer. (B) Representative three-dimensional model of GDF15 (cyan color) in complex with its receptor GFRAL (hot pink) as deduced by crystallographic studies; the interacting residues are shown in a ball and stick model. (C) Three-dimensional representation of the GDF15 and GFRAL complex. Dimeric GDF15 binds with two GFRAL molecules, providing multiple binding sites to target with small-molecule inhibitors. (D) Enlarged view of hydrogen bond-forming interfacial residues of the GDF15-GFRAL complex as shown in a ball and stick model. These interactions help in drug design and discovery. (E) Three-dimensional view of two molecules of monoclonal antibodies interacting with GFRAL, forming an antibody-protein complex. The interacting interfaces of the antibody heavy and light chains with the GFRAL complex are shown in an enlarged view (Site-I and Site-II). This three-dimensional structure of the antibody-GFRAL complex highlights two different binding sites (site-I and site-II) of GFRAL that could be exploited to develop specific inhibitors of GDF15-GFRAL interactions. The 3D structural model was generated using PyMOL, and structure coordinates were taken from Protein Data Bank (PDB ID: 5VZ3 & 6WMW).