Crucial roles of Glu60 in human neuroglobin as a guanine nucleotide dissociation inhibitor and neuroprotective agent

PLoS One. 2013 Dec 23;8(12):e83698. doi: 10.1371/journal.pone.0083698. eCollection 2013.

Abstract

Mammalian neuroglobin (Ngb) protects neuronal cells under conditions of oxidative stress. We previously showed that human Ngb acts as a guanine nucleotide dissociation inhibitor (GDI) for the α-subunits of heterotrimeric Gi/o proteins and inhibits reductions in cAMP concentration, leading to protection against cell death. In the present study, we created human E60Q Ngb mutant and clarified that Glu60 of human Ngb is a crucial residue for its GDI and neuroprotective activities. Moreover, we investigated structural and functional properties of several human Ngb mutants and demonstrated that the neuroprotective effect of human Ngb is due to its GDI activity and not due to its scavenging activity against reactive oxygen species.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Cell Differentiation
  • Cell Line
  • Globins / chemistry*
  • Globins / genetics
  • Globins / metabolism*
  • Glutamic Acid*
  • Guanine Nucleotide Dissociation Inhibitors / chemistry*
  • Guanine Nucleotide Dissociation Inhibitors / genetics
  • Guanine Nucleotide Dissociation Inhibitors / metabolism*
  • Humans
  • Mutation
  • Nerve Tissue Proteins / chemistry*
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*
  • Neuroglobin
  • Neurons / cytology

Substances

  • Guanine Nucleotide Dissociation Inhibitors
  • Nerve Tissue Proteins
  • Neuroglobin
  • Glutamic Acid
  • Globins

Grants and funding

This work was supported in part by the PRESTO program of Japan Science and Technology (JST) (to K.W.), the Fuji Foundation for Protein Research (to K.W.), and a Grant-in-Aid for Scientific Research on Innovative Areas (No. 23117704) (to K.W.) from the Ministry of Education, Culture, Sports, Science and Technology of Japan. S.W. was supported by the JSPS Research Fellowships for Young Scientists. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.