Structural analysis of the stable form of fibroblast growth
factor 2 - FGF2-STAB

J 2024

Structural analysis of the stable form of fibroblast growth factor 2 - FGF2-STAB

DE LA BOURDONNAYE, Gabin; Martin MAREK; Tereza GHAZALOVÁ; Jiří DAMBORSKÝ; Petr PACHL et al.

Základní údaje

Originální název

Structural analysis of the stable form of fibroblast growth factor 2 - FGF2-STAB

Autoři

DE LA BOURDONNAYE, Gabin; Martin MAREK; Tereza GHAZALOVÁ; Jiří DAMBORSKÝ; Petr PACHL; Jiri BRYNDA; Veronika ŠTĚPÁNKOVÁ a Radka CHALOUPKOVÁ

Vydání

Journal of Structural Biology: X, AMSTERDAM, ELSEVIER, 2024, 2590-1524

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

10610 Biophysics

Stát vydavatele

Nizozemské království

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 5.100

Označené pro přenos do RIV

Ano

Kód RIV

RIV/00216224:14310/24:00138632

Organizační jednotka

Přírodovědecká fakulta

Klíčová slova anglicky

Stabilized fibroblast growth factor 2; X-ray structural analysis; Protein flexibility

Štítky

14314010, 143180, rivok

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 25. 2. 2025 17:12, Mgr. Michaela Hylsová, Ph.D.

Anotace

V originále

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 FGF2STAB solved at 1.3 & Aring; 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.

Návaznosti

GA22-09853S, projekt VaV

Název: Analýza vzniku nových proteinových funkcí v rámci rodiny halogenalkan dehalogenas

Investor: Grantová agentura ČR, Analýza vzniku nových proteinových funkcí v rámci rodiny halogenalkan dehalogenas

LM2023055, projekt VaV

Název: Česká národní infrastruktura pro biologická data

Investor: Ministerstvo školství, mládeže a tělovýchovy ČR, ELIXIR-CZ: Česká národní infrastruktura pro biologická data

90269, velká výzkumná infrastruktura

Název: RECETOX RI II

Citovat

DE LA BOURDONNAYE, Gabin; Martin MAREK; Tereza GHAZALOVÁ; Jiří DAMBORSKÝ; Petr PACHL; Jiri BRYNDA; Veronika ŠTĚPÁNKOVÁ a Radka CHALOUPKOVÁ. Structural analysis of the stable form of fibroblast growth factor 2 - FGF2-STAB. Journal of Structural Biology: X. AMSTERDAM: ELSEVIER, 2024, roč. 10, December 2024, s. 1-8. ISSN 2590-1524. Dostupné z: https://doi.org/10.1016/j.yjsbx.2024.100112.

@article{2471448,
   author = {de La Bourdonnaye, Gabin and Marek, Martin and Ghazalová, Tereza and Damborský, Jiří and Pachl, Petr and Brynda, Jiri and Štěpánková, Veronika and Chaloupková, Radka},
   article_location = {AMSTERDAM},
   article_number = {December 2024},
   doi = {https://doi.org/10.1016/j.yjsbx.2024.100112},
   keywords = {Stabilized fibroblast growth factor 2; X-ray structural analysis; Protein flexibility},
   language = {eng},
   issn = {2590-1524},
   journal = {Journal of Structural Biology: X},
   title = {Structural analysis of the stable form of fibroblast growth factor 2 - FGF2-STAB},
   url = {https://www.sciencedirect.com/science/article/pii/S2590152424000175?via%3Dihub},
   volume = {10},
   year = {2024}
}

TY  - JOUR
ID  - 2471448
AU  - de La Bourdonnaye, Gabin - Marek, Martin - Ghazalová, Tereza - Damborský, Jiří - Pachl, Petr - Brynda, Jiri - Štěpánková, Veronika - Chaloupková, Radka
PY  - 2024
TI  - Structural analysis of the stable form of fibroblast growth factor 2 - FGF2-STAB
JF  - Journal of Structural Biology: X
VL  - 10
IS  - December 2024
SP  - 1-8
EP  - 1-8
PB  - ELSEVIER
SN  - 25901524
KW  - Stabilized fibroblast growth factor 2
KW  - X-ray structural analysis
KW  - Protein flexibility
UR  - https://www.sciencedirect.com/science/article/pii/S2590152424000175?via%3Dihub
N2  - 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 FGF2STAB solved at 1.3 & Aring; 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.
ER  -

DE LA BOURDONNAYE, Gabin; Martin MAREK; Tereza GHAZALOVÁ; Jiří DAMBORSKÝ; Petr PACHL; Jiri BRYNDA; Veronika ŠTĚPÁNKOVÁ a Radka CHALOUPKOVÁ. Structural analysis of the stable form of fibroblast growth factor 2 - FGF2-STAB. \textit{Journal of Structural Biology: X}. AMSTERDAM: ELSEVIER, 2024, roč.~10, December 2024, s.~1-8. ISSN~2590-1524. Dostupné z: https://doi.org/10.1016/j.yjsbx.2024.100112.

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