8OM6

Crystal structure of FGF2-STAB, a stable variant of human fibroblast growth factor 2

Summary for 8OM6

• Entry DOI: 10.2210/pdb8om6/pdb
• Descriptor: Fibroblast growth factor 2 (2 entities in total)
• Functional Keywords: hormone/growth factor, mitogen, cytokine
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 1
• Total formula weight: 19531.27

Authors

Marek, M.,Chaloupkova, R.,de La Bourdonnaye, G. (deposition date: 2023-03-31, release date: 2024-03-06, Last modification date: 2025-03-19)

Primary citation

de La Bourdonnaye, G.,Marek, M.,Ghazalova, T.,Damborsky, J.,Pachl, P.,Brynda, J.,Stepankova, V.,Chaloupkova, R.
Structural analysis of the stable form of fibroblast growth factor 2 - FGF2-STAB.
J Struct Biol X, 10:100112-100112, 2024

PubMed Abstract: Fibroblast growth factor 2 (FGF2) is a signaling protein that plays a significant role in tissue development and repair. FGF2 binds to fibroblast growth factor receptors (FGFRs) alongside its co-factor heparin, which protects FGF2 from degradation. The binding between FGF2 and FGFRs induces intracellular signaling pathways such as RAS-MAPK, PI3K-AKT, and STAT. FGF2 has strong potential for application in cell culturing, wound healing, and cosmetics but the potential is severely limited by its low protein stability. The thermostable variant FGF2-STAB was constructed by computer-assisted protein engineering to overcome the natural limitation of FGF2. Previously reported characterization of FGF2-STAB revealed an enhanced ability to induce MAP/ERK signaling while having a lower dependence on heparin when compared with FGF2-wt. Here we report the crystal structure of FGF2-STAB solved at 1.3 Å resolution. Protein stabilization is achieved by newly formed hydrophobic interactions, polar contacts, and one additional hydrogen bond. The overall structure of FGF2-STAB is similar to FGF2-wt and does not reveal information on the experimentally observed lower dependence on heparin. A noticeable difference in flexibility in the receptor binding region can explain the differences in signaling between FGF2-STAB and its wild-type counterpart. Our structural analysis provided molecular insights into the stabilization and unique biological properties of FGF2-STAB.

PubMed: 39512606
DOI: 10.1016/j.yjsbx.2024.100112

Experimental method

X-RAY DIFFRACTION (1.31 Å)