Dispersive interactions govern strong thermal stability of a protein

VONDRÁŠEK, Jiří, Tomáš KUBAŘ, Francis E. JENNEY, JR., Michael W.W. ADAMS, Milan KOŽÍŠEK, Jiří ČERNÝ, Vladimír SKLENÁŘ a Pavel HOBZA. Dispersive interactions govern strong thermal stability of a protein. Chemistry- A European Journal. roč. 13, č. 32, s. 9022-9027. ISSN 0947-6539. 2007.

Základní údaje

• Originální název: Dispersive interactions govern strong thermal stability of a protein
• Název česky: Disperzní interakce determinují velkou termální stabilitu proteinu
• Autoři: VONDRÁŠEK, Jiří (203 Česká republika), Tomáš KUBAŘ (203 Česká republika), Francis E. JENNEY, JR. (840 Spojené státy), Michael W.W. ADAMS (840 Spojené státy), Milan KOŽÍŠEK (203 Česká republika), Jiří ČERNÝ (203 Česká republika), Vladimír SKLENÁŘ (203 Česká republika, garant) a Pavel HOBZA (203 Česká republika).
• Vydání: Chemistry- A European Journal, 2007, 0947-6539.

Další údaje

• Originální jazyk: angličtina
• Typ výsledku: Článek v odborném periodiku
• Obor: 10610 Biophysics
• Stát vydavatele: Německo
• Utajení: není předmětem státního či obchodního tajemství
• WWW: URL
• Impakt faktor: Impact factor: 5.330
• Kód RIV: RIV/00216224:14310/07:00022789
• Organizační jednotka: Přírodovědecká fakulta
• Klíčová slova anglicky: ab initio calculations; hydrophobic core; hydrophobic effect; molecular modeling; NMR spectroscopy
• Štítky: Ab initio calculations, hydrophobic core, hydrophobic effect, molecular modeling, NMR Spectroscopy
• Příznaky: Mezinárodní význam, Recenzováno

Anotace

Rubredoxin from the hyperthermophile Pyrococcus furiosus (Pf Rd) is an extremely thermostable protein, which makes it an attractive subject of protein folding and stability studies. A fundamental question arises of what the reason for such extreme stability is and how it can be elucidated from a complex set of inter-atomic interactions. We addressed this issue first theoretically through a computational analysis of the hydrophobic core of the protein and its mutants including the interactions taking place inside the core. Here we show that a single mutation of one phenylalanine's residues inside the protein's hydrophobic core results in a dramatic decrease in its thermal stability. The calculated unfolding Gibbs energy as well as the stabilisation energy differences between a few core residues follow the same trend as the melting temperature of protein variants determined experimentally by microcalorimetry measurements. NMR experiments have shown that the only part of the protein affected by mutation is the reasonably rearranged hydrophobic core. It is hence concluded that stabilisation energies, which are dominated by London dispersion, represent the main source of stability of this protein.

Anotace česky

Rubredoxin from the hyperthermophile Pyrococcus furiosus (Pf Rd) is an extremely thermostable protein, which makes it an attractive subject of protein folding and stability studies. A fundamental question arises of what the reason for such extreme stability is and how it can be elucidated from a complex set of inter-atomic interactions. We addressed this issue first theoretically through a computational analysis of the hydrophobic core of the protein and its mutants including the interactions taking place inside the core. Here we show that a single mutation of one phenylalanine's residues inside the protein's hydrophobic core results in a dramatic decrease in its thermal stability. The calculated unfolding Gibbs energy as well as the stabilisation energy differences between a few core residues follow the same trend as the melting temperature of protein variants determined experimentally by microcalorimetry measurements. NMR experiments have shown that the only part of the protein affected by mutation is the reasonably rearranged hydrophobic core. It is hence concluded that stabilisation energies, which are dominated by London dispersion, represent the main source of stability of this protein.

Návaznosti

• LC06030, projekt VaV: Název: Biomolekulární centrum

Investor: Ministerstvo školství, mládeže a tělovýchovy ČR, Biomolekulární centrum

• MSM0021622413, záměr: Název: Proteiny v metabolismu a při interakci organismů s prostředím

Investor: Ministerstvo školství, mládeže a tělovýchovy ČR, Proteiny v metabolismu a při interakci organismů s prostředím