High resolution

Module 4: Figure HIF structure

The structure and activation of hypoxia-inducible factor 1α (HIF-1α).

The O2-sensitive hypoxia-inducible factor 1α (HIF-1α) has a basic helix–loop–helix (HLH) domain that enables it to form a heterodimer with the O2-insensitive HIF-1β subunit to form the functional transcription factor. The activity of HIF-1α depends on the hydroxylation of proline residues at 402 and 564 and an asparagine residue at 803. The proline residues are hydroxylated by a prolyl hydroxylase (PHD2), whereas a factor inhibiting HIF (FIH) hydroxylates the asparagine residue. These hydroxy groups provide binding sites for the von Hippel–Lindau (VHL) protein that directs HIF-1α to the proteasomal degradation pathway and for p300 that regulates its transcriptional activity. See Module 4: Figure HIF activation for details of how O2 regulates the activity of HIF-1α.