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

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Details

Original languageEnglish
Pages (from-to)2721-2730
Number of pages10
JournalJournal of Physical Chemistry Part B
Volume120
Issue number10
DOIs
Publication statusPublished - 17 Mar 2016
Publication typeA1 Journal article-refereed

Abstract

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.

Publication forum classification

Field of science, Statistics Finland