Dynamic structure mediates halophilic adaptation of a DNA polymerase from the deep-sea brines of the Red Sea

Masateru Takahashi, Etsuko Takahashi, Luay Joudeh, Monica Marini, Gobind Das, Mohamed Elshenawy, Anastassja Gespers (Akal), Kosuke Sakashita, Intikhab Alam, Muhammad Tehseen, Mohamed Abdelmaboud Sobhy, Ulrich Stingl, Jasmeen Merzaban, Enzo M. Di Fabrizio, Samir Hamdan

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

The deep-sea brines of the Red Sea are remote and unexplored environments characterized by high temperatures, anoxic water, and elevated concentrations of salt and heavy metals. This environment provides a rare system to study the interplay between halophilic and thermophilic adaptation in biologic macromolecules. The present article reports the first DNA polymerase with halophilic and thermophilic features. Biochemical and structural analysis by Raman and circular dichroism spectroscopy showed that the charge distribution on the protein’s surface mediates the structural balance between stability for thermal adaptation and flexibility for counteracting the salt-induced rigid and nonfunctional hydrophobic packing. Salt bridge interactions via increased negative and positive charges contribute to structural stability. Salt tolerance, conversely, is mediated by a dynamic structure that becomes more fixed and functional with increasing salt concentration. We propose that repulsive forces among excess negative charges, in addition to a high percentage of negatively charged random coils, mediate this structural dynamism. This knowledge enabled us to engineer a halophilic version of KOD DNA polymerase.—Takahashi, M., Takahashi, E., Joudeh, L. I., Marini, M., Das, G., Elshenawy, M. M., Akal, A., Sakashita, K., Alam, I., Tehseen, M., Sobhy, M. A., Stingl, U., Merzaban, J. S., Di Fabrizio, E., Hamdan, S. M. Dynamic structure mediates halophilic adaptation of a DNA polymerase from the deep-sea brines of the Red Sea.
Original languageEnglish (US)
Pages (from-to)3346-3360
Number of pages15
JournalThe FASEB Journal
Volume32
Issue number6
DOIs
StatePublished - Jan 24 2018

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