Limits...
Unsaturated fatty acids as high-affinity ligands of the C-terminal Per-ARNT-Sim domain from the Hypoxia-inducible factor 3α.

Fala AM, Oliveira JF, Adamoski D, Aricetti JA, Dias MM, Dias MV, Sforça ML, Lopes-de-Oliveira PS, Rocco SA, Caldana C, Dias SM, Ambrosio AL - Sci Rep (2015)

Bottom Line: Hypoxia-inducible transcription factors (HIF) form heterodimeric complexes that mediate cell responses to hypoxia.The oxygen-dependent stability and activity of the HIF-α subunits is traditionally associated to post-translational modifications such as hydroxylation, acetylation, ubiquitination, and phosphorylation.Here we report novel evidence showing that unsaturated fatty acids are naturally occurring, non-covalent structural ligands of HIF-3α, thus providing the initial framework for exploring its exceptional role as a lipid sensor under hypoxia.

View Article: PubMed Central - PubMed

Affiliation: Laboratório Nacional de Biociências, Centro Nacional de Pesquisa em Energia e Materiais, Campinas, SP, Brazil, 13083-100.

ABSTRACT
Hypoxia-inducible transcription factors (HIF) form heterodimeric complexes that mediate cell responses to hypoxia. The oxygen-dependent stability and activity of the HIF-α subunits is traditionally associated to post-translational modifications such as hydroxylation, acetylation, ubiquitination, and phosphorylation. Here we report novel evidence showing that unsaturated fatty acids are naturally occurring, non-covalent structural ligands of HIF-3α, thus providing the initial framework for exploring its exceptional role as a lipid sensor under hypoxia.

No MeSH data available.


Related in: MedlinePlus

Characterization of the lipids bound to PASb-3α.(a) Two neutral lipids (yellow bands on the iodine vapor stained plate) and two phosphorous-containing lipids (blue bands over white background) were carried over by the purified protein samples. The two phospholipids were identified as 18:1-lysophospholipds. (b) Free oleic and linoleic acids bind with low-nanomolar affinity to delipidated PASb-3α, suggesting that unsaturation is a mandatory feature for the partner fatty acid and, as unsaturation accumulates, the higher the affinity for the protein. (c) Boltzmann distributions representing the canonical ensembles of fatty acid desolvation. The estimated entropies decrease as the degree of unsaturation increase. Crossed-circles over the curves point out the frequency of putative bound-state enthalpy into the distribution.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4522956&req=5

f2: Characterization of the lipids bound to PASb-3α.(a) Two neutral lipids (yellow bands on the iodine vapor stained plate) and two phosphorous-containing lipids (blue bands over white background) were carried over by the purified protein samples. The two phospholipids were identified as 18:1-lysophospholipds. (b) Free oleic and linoleic acids bind with low-nanomolar affinity to delipidated PASb-3α, suggesting that unsaturation is a mandatory feature for the partner fatty acid and, as unsaturation accumulates, the higher the affinity for the protein. (c) Boltzmann distributions representing the canonical ensembles of fatty acid desolvation. The estimated entropies decrease as the degree of unsaturation increase. Crossed-circles over the curves point out the frequency of putative bound-state enthalpy into the distribution.

Mentions: Aiming at experimental confirmation of the identity of the proposed monoacylglycerol, the hydrophobic fraction was carefully isolated from pure protein samples in solution and analyzed by thin-layer chromatography (TLC). By applying two mobile phases distinct in polarity, as well as dual staining to allow for differential detection of neutral and phosphorous-containing lipids13, we surprisingly observed the dominant presence of two neutral lipids and two phospholipids as ligands of PASb-3α (Fig. 2a).


Unsaturated fatty acids as high-affinity ligands of the C-terminal Per-ARNT-Sim domain from the Hypoxia-inducible factor 3α.

Fala AM, Oliveira JF, Adamoski D, Aricetti JA, Dias MM, Dias MV, Sforça ML, Lopes-de-Oliveira PS, Rocco SA, Caldana C, Dias SM, Ambrosio AL - Sci Rep (2015)

Characterization of the lipids bound to PASb-3α.(a) Two neutral lipids (yellow bands on the iodine vapor stained plate) and two phosphorous-containing lipids (blue bands over white background) were carried over by the purified protein samples. The two phospholipids were identified as 18:1-lysophospholipds. (b) Free oleic and linoleic acids bind with low-nanomolar affinity to delipidated PASb-3α, suggesting that unsaturation is a mandatory feature for the partner fatty acid and, as unsaturation accumulates, the higher the affinity for the protein. (c) Boltzmann distributions representing the canonical ensembles of fatty acid desolvation. The estimated entropies decrease as the degree of unsaturation increase. Crossed-circles over the curves point out the frequency of putative bound-state enthalpy into the distribution.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4522956&req=5

f2: Characterization of the lipids bound to PASb-3α.(a) Two neutral lipids (yellow bands on the iodine vapor stained plate) and two phosphorous-containing lipids (blue bands over white background) were carried over by the purified protein samples. The two phospholipids were identified as 18:1-lysophospholipds. (b) Free oleic and linoleic acids bind with low-nanomolar affinity to delipidated PASb-3α, suggesting that unsaturation is a mandatory feature for the partner fatty acid and, as unsaturation accumulates, the higher the affinity for the protein. (c) Boltzmann distributions representing the canonical ensembles of fatty acid desolvation. The estimated entropies decrease as the degree of unsaturation increase. Crossed-circles over the curves point out the frequency of putative bound-state enthalpy into the distribution.
Mentions: Aiming at experimental confirmation of the identity of the proposed monoacylglycerol, the hydrophobic fraction was carefully isolated from pure protein samples in solution and analyzed by thin-layer chromatography (TLC). By applying two mobile phases distinct in polarity, as well as dual staining to allow for differential detection of neutral and phosphorous-containing lipids13, we surprisingly observed the dominant presence of two neutral lipids and two phospholipids as ligands of PASb-3α (Fig. 2a).

Bottom Line: Hypoxia-inducible transcription factors (HIF) form heterodimeric complexes that mediate cell responses to hypoxia.The oxygen-dependent stability and activity of the HIF-α subunits is traditionally associated to post-translational modifications such as hydroxylation, acetylation, ubiquitination, and phosphorylation.Here we report novel evidence showing that unsaturated fatty acids are naturally occurring, non-covalent structural ligands of HIF-3α, thus providing the initial framework for exploring its exceptional role as a lipid sensor under hypoxia.

View Article: PubMed Central - PubMed

Affiliation: Laboratório Nacional de Biociências, Centro Nacional de Pesquisa em Energia e Materiais, Campinas, SP, Brazil, 13083-100.

ABSTRACT
Hypoxia-inducible transcription factors (HIF) form heterodimeric complexes that mediate cell responses to hypoxia. The oxygen-dependent stability and activity of the HIF-α subunits is traditionally associated to post-translational modifications such as hydroxylation, acetylation, ubiquitination, and phosphorylation. Here we report novel evidence showing that unsaturated fatty acids are naturally occurring, non-covalent structural ligands of HIF-3α, thus providing the initial framework for exploring its exceptional role as a lipid sensor under hypoxia.

No MeSH data available.


Related in: MedlinePlus