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Stability and Function at High Temperature. What Makes a Thermophilic GTPase Different from Its Mesophilic Homologue

Tutkimustuotosvertaisarvioitu

Yksityiskohdat

AlkuperäiskieliEnglanti
Sivut2721-2730
Sivumäärä10
JulkaisuJournal of Physical Chemistry Part B
Vuosikerta120
Numero10
DOI - pysyväislinkit
TilaJulkaistu - 17 maaliskuuta 2016
OKM-julkaisutyyppiA1 Alkuperäisartikkeli

Tiivistelmä

Comparing homologous enzymes adapted to different thermal environments AIDS to shed light on their delicate stability/function trade-off. Protein mechanical rigidity was postulated to secure stability and high-temperature functionality of thermophilic proteins. In this work, we challenge the corresponding-state principle for a pair of homologous GTPase domains by performing extensive molecular dynamics simulations, applying conformational and kinetic clustering, as well as exploiting an enhanced sampling technique (REST2). While it was formerly shown that enhanced protein flexibility and high temperature stability can coexist in the apo hyperthermophilic variant, here we focus on the holo states of both homologues by mimicking the enzymatic turnover. We clearly show that the presence of the ligands affects the conformational landscape visited by the proteins, and that the corresponding state principle applies for some functional modes. Namely, in the hyperthermophilic species, the flexibility of the effector region ensuring long-range communication and of the P-loop modulating ligand binding are recovered only at high temperature.

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