The hypoxic regulator of sterol synthesis Nro1 is a nuclear import adaptorThe hypoxic regulator of sterol synthesis Nro1 is a nuclear import adaptor

Structural highlights

3msv is a 2 chain structure with sequence from Cbs 356. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Gene:SPCC4B3.07 (CBS 356)
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[ETT1_SCHPO] Required for correct translation termination (By similarity). Positive regulator of the stability of the N-terminal transcription factor domain (Sre1N) of sre1 which is released from the membrane and enters the nucleus to activate hypoxic gene expression. Acts also as a direct inhibitor of ofd1. Functions probably by inhibiting the ability of the ofd1 to accelerate Sre1N degradation in absence of oxygen.[1] [2]

Publication Abstract from PubMed

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 A resolution shows an all-alpha-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.

The hypoxic regulator of sterol synthesis nro1 is a nuclear import adaptor.,Yeh TL, Lee CY, Amzel LM, Espenshade PJ, Bianchet MA Structure. 2011 Apr 13;19(4):503-14. PMID:21481773[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

  1. Chen XQ, Du X, Liu J, Balasubramanian MK, Balasundaram D. Identification of genes encoding putative nucleoporins and transport factors in the fission yeast Schizosaccharomyces pombe: a deletion analysis. Yeast. 2004 Apr 30;21(6):495-509. PMID:15116432 doi:http://dx.doi.org/10.1002/yea.1115
  2. Lee CY, Stewart EV, Hughes BT, Espenshade PJ. Oxygen-dependent binding of Nro1 to the prolyl hydroxylase Ofd1 regulates SREBP degradation in yeast. EMBO J. 2009 Jan 21;28(2):135-43. doi: 10.1038/emboj.2008.271. PMID:19158663 doi:http://dx.doi.org/10.1038/emboj.2008.271
  3. Yeh TL, Lee CY, Amzel LM, Espenshade PJ, Bianchet MA. The hypoxic regulator of sterol synthesis nro1 is a nuclear import adaptor. Structure. 2011 Apr 13;19(4):503-14. PMID:21481773 doi:10.1016/j.str.2011.01.017

3msv, resolution 2.18Å

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA