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X-Ray Crystallography to Study the Oligomeric State Transition of the Thermotoga maritima M42 Aminopeptidase TmPep1050
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X-Ray Crystallography to Study the Oligomeric State Transition of the Thermotoga maritima M42 Aminopeptidase TmPep1050

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Structure of the catalytic phosphatase domain of MTMR8: implications for dimerization, membrane association and

Ki Young Yoo1, Ji Young Son1, Jee Un Lee1

  • 1Department of Chemistry, Konkuk University, 1 Hwayang-dong, Gwangjin-gu, Seoul 143-701, Republic of Korea.

Acta Crystallographica. Section D, Biological Crystallography
|July 7, 2015
PubMed

Insights

The crystal structure of MTMR8 reveals a novel dimerization mode for myotubularin-related proteins. This research clarifies how MTMR8

Area of Science:

  • Biochemistry
  • Structural Biology
  • Molecular Biology

Background:

  • Myotubularin-related proteins (MTMRs) are phosphoinositide phosphatases regulating cellular functions through dimerization.
  • Understanding MTMR family interactions is crucial for elucidating their roles in various biological processes.

Purpose of the Study:

  • To determine the crystal structure of the phosphatase domain of MTMR8.
  • To investigate the dimerization mechanism and substrate interaction of MTMR8.
  • To explore the regulation of MTMR8 catalytic activity.

Main Methods:

  • X-ray crystallography to obtain the structure of the MTMR8 phosphatase domain.
  • Structural comparison with other MTMR family members.
  • Site-directed mutagenesis studies to probe residue function.
  • Biochemical assays to assess catalytic activity and regulation.

Main Results:

  • The crystal structure reveals a novel twofold symmetric dimer of the MTMR8 phosphatase domain.
  • Conformational differences in interaction loops suggest distinct PH-GRAM domain binding across MTMR family members.
  • Lys255 in MTMR8 interacts with the diacylglycerol substrate, analogous to MTMR2, despite different positioning.
  • MTMR8 catalytic activity is inhibited by oxidation and restored by reduction, indicating a non-disulfide bond protective mechanism.

Conclusions:

  • The MTMR8 crystal structure provides insights into a unique dimerization interface within the MTMR family.
  • Structural variations highlight differential interactions with the PH-GRAM domain among MTMR proteins.
  • MTMR8 activity is redox-sensitive, regulated by an oxidation-protective mechanism independent of disulfide bonds.
Keywords:
MTMR8myotubularinphosphatasephosphoinositideredox regulation

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