The hypoxic regulator of sterol synthesis nro1 is a nuclear import adaptor

Structure. 2011 Apr 13;19(4):503-14. doi: 10.1016/j.str.2011.01.017.

Abstract

Fission yeast protein Sre1, the homolog of the mammalian sterol regulatory element-binding protein (SREBP), is a hypoxic transcription factor required for sterol homeostasis and low-oxygen growth. Nro1 regulates the stability of the N-terminal transcription factor domain of Sre1 (Sre1N) by inhibiting the action of the prolyl 4-hydroxylase-like Ofd1 in an oxygen-dependent manner. The crystal structure of Nro1 determined at 2.2 Å resolution shows an all-α-helical fold that can be divided into two domains: a small N-terminal domain, and a larger C-terminal HEAT-repeat domain. Follow-up studies showed that Nro1 defines a new class of nuclear import adaptor that functions both in Ofd1 nuclear localization and in the oxygen-dependent inhibition of Ofd1 to control the hypoxic response.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Active Transport, Cell Nucleus
  • Amino Acid Sequence
  • Anaerobiosis
  • Cell Nucleus / metabolism*
  • Crystallography, X-Ray
  • Immunoprecipitation
  • Models, Molecular
  • Molecular Sequence Data
  • Mutation
  • Nuclear Proteins / chemistry*
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism
  • Oxygen / metabolism
  • Procollagen-Proline Dioxygenase / chemistry
  • Procollagen-Proline Dioxygenase / genetics
  • Procollagen-Proline Dioxygenase / metabolism
  • Protein Binding
  • Protein Structure, Secondary*
  • Schizosaccharomyces pombe Proteins / chemistry*
  • Schizosaccharomyces pombe Proteins / genetics
  • Schizosaccharomyces pombe Proteins / metabolism
  • Sequence Homology, Amino Acid
  • Sterols / biosynthesis*
  • Two-Hybrid System Techniques

Substances

  • Nro1 protein, S pombe
  • Nuclear Proteins
  • Schizosaccharomyces pombe Proteins
  • Sre1 protein, S pombe
  • Sterols
  • Procollagen-Proline Dioxygenase
  • Oxygen