Structural analysis of the stable form of fibroblast growth factor 2 – FGF2-STAB
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 intracel...
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| Language: | English |
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Elsevier
2024-12-01
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| Series: | Journal of Structural Biology: X |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2590152424000175 |
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| author | Gabin de La Bourdonnaye Martin Marek Tereza Ghazalova Jiri Damborsky Petr Pachl Jiri Brynda Veronika Stepankova Radka Chaloupkova |
| author_facet | Gabin de La Bourdonnaye Martin Marek Tereza Ghazalova Jiri Damborsky Petr Pachl Jiri Brynda Veronika Stepankova Radka Chaloupkova |
| author_sort | Gabin de La Bourdonnaye |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-4ac9464e85cb425fb008c0c9b8444e8b |
| institution | Kabale University |
| issn | 2590-1524 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Structural Biology: X |
| spelling | doaj-art-4ac9464e85cb425fb008c0c9b8444e8b2024-12-12T05:22:35ZengElsevierJournal of Structural Biology: X2590-15242024-12-0110100112Structural analysis of the stable form of fibroblast growth factor 2 – FGF2-STABGabin de La Bourdonnaye0Martin Marek1Tereza Ghazalova2Jiri Damborsky3Petr Pachl4Jiri Brynda5Veronika Stepankova6Radka Chaloupkova7Loschmidt Laboratories, Department of Experimental Biology and RECETOX, Faculty of Science, Masaryk University, Brno, Czech Republic; Enantis Ltd., Biotechnology Incubator INBIT, Brno, Czech RepublicLoschmidt Laboratories, Department of Experimental Biology and RECETOX, Faculty of Science, Masaryk University, Brno, Czech Republic; International Clinical Research Center, St. Anne’s University Hospital, Brno, Czech RepublicEnantis Ltd., Biotechnology Incubator INBIT, Brno, Czech RepublicLoschmidt Laboratories, Department of Experimental Biology and RECETOX, Faculty of Science, Masaryk University, Brno, Czech Republic; International Clinical Research Center, St. Anne’s University Hospital, Brno, Czech RepublicInstitute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Prague, Czech RepublicInstitute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Prague, Czech RepublicEnantis Ltd., Biotechnology Incubator INBIT, Brno, Czech RepublicLoschmidt Laboratories, Department of Experimental Biology and RECETOX, Faculty of Science, Masaryk University, Brno, Czech Republic; Enantis Ltd., Biotechnology Incubator INBIT, Brno, Czech Republic; Corresponding author.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.http://www.sciencedirect.com/science/article/pii/S2590152424000175Stabilized fibroblast growth factor 2X-ray structural analysisProtein flexibility |
| spellingShingle | Gabin de La Bourdonnaye Martin Marek Tereza Ghazalova Jiri Damborsky Petr Pachl Jiri Brynda Veronika Stepankova Radka Chaloupkova Structural analysis of the stable form of fibroblast growth factor 2 – FGF2-STAB Journal of Structural Biology: X Stabilized fibroblast growth factor 2 X-ray structural analysis Protein flexibility |
| title | Structural analysis of the stable form of fibroblast growth factor 2 – FGF2-STAB |
| title_full | Structural analysis of the stable form of fibroblast growth factor 2 – FGF2-STAB |
| title_fullStr | Structural analysis of the stable form of fibroblast growth factor 2 – FGF2-STAB |
| title_full_unstemmed | Structural analysis of the stable form of fibroblast growth factor 2 – FGF2-STAB |
| title_short | Structural analysis of the stable form of fibroblast growth factor 2 – FGF2-STAB |
| title_sort | structural analysis of the stable form of fibroblast growth factor 2 fgf2 stab |
| topic | Stabilized fibroblast growth factor 2 X-ray structural analysis Protein flexibility |
| url | http://www.sciencedirect.com/science/article/pii/S2590152424000175 |
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