Pressure Adaptations in Deep-Sea Moritella Dihydrofolate Reductases: Compressibility versus Stability

Area of Science:

• Biochemistry
• Molecular Biology
• Structural Biology

Background:

• Piezophilic proteins adapt to high pressure, often through increased compressibility and larger internal cavities.
• However, larger cavities can paradoxically decrease protein stability under pressure.

Purpose of the Study:

• To compare the compressibility and structural adaptations of dihydrofolate reductase (DHFR) from moderate (Moritella profunda, Mp) and hyperpiezophilic (Moritella yayanosii, My) bacteria.
• To investigate how structural differences in MyDHFR contribute to adaptation at extreme depths.

Main Methods:

• Molecular dynamics simulations were employed to analyze the average properties and compressibility of MpDHFR and MyDHFR.
• Quasiharmonic analysis and cavity analysis were performed to assess structural features and internal voids.

Main Results:

• Both MpDHFR and MyDHFR exhibit similar compressibility, contrary to some previous findings.
• MyDHFR possesses unique mutations near cavities, with Tyr103 forming a hydrogen bond that blocks a surface-to-interior pathway present in MpDHFR.
• This structural adaptation in MyDHFR appears to prevent water from entering internal cavities.

Conclusions:

• Moritella DHFR variants are generally adapted for high-pressure environments due to their compressibility.
• Adaptations in MyDHFR, specifically the blocking of internal cavities, are crucial for survival at extreme oceanic depths by preventing water ingress.