8HE0

Crystal structure of importin-alpha1 bound to the HIF-1alpha nuclear localization signal (wild-type)

Summary for 8HE0

• Entry DOI: 10.2210/pdb8he0/pdb
• Descriptor: Importin subunit alpha-1, Hypoxia-inducible factor 1-alpha (3 entities in total)
• Functional Keywords: nls, transport protein
• Biological source: Mus musculus (house mouse); More
• Total number of polymer chains: 2
• Total formula weight: 51119.51

Authors

Matsuura, Y. (deposition date: 2022-11-07, release date: 2023-02-22, Last modification date: 2023-11-29)

Primary citation

Matsuura, Y.,Miyawaki, K.
Structures of importin-alpha bound to the wild-type and an internal deletion mutant of the bipartite nuclear localization signal of HIF-1 alpha.
Biochem.Biophys.Res.Commun., 652:1-5, 2023

PubMed Abstract: Hypoxia-inducible factor 1 (HIF-1) is a heterodimeric transcription factor that plays an important role as a master regulator of oxygen homeostasis. The activity of HIF-1 is regulated in part by dynamic intracellular trafficking of its α subunit (HIF-1α) that can shuttle between the nucleus and cytoplasm. It has been shown that nuclear localization of HIF-1α requires a variant of classic nuclear localization signal (NLS) and that an internal deletion of the amino acid residues (residues 724-751) in the NLS almost abolish the nuclear localization. Here we report the X-ray crystal structure of the nuclear import adaptor importin-α1 bound to the wild-type HIF-1α NLS at 1.8 Å resolution and of importin-α1 bound to the Δ724-751 mutant of the HIF-1α NLS at 1.9 Å resolution. In the wild-type structure, two basic clusters in the HIF-1α NLS made extensive interactions with importin-α1 on two sites (the major site and the minor site). In the mutant structure, the NLS residues still interacted extensively with the major site on importin-α1, but the interactions with the minor site were not observed. The structural data, together with computational analyses of binding free energies, indicate that the loss of the minor-site interactions inhibit nuclear accumulation of HIF-1α.

PubMed: 36806083
DOI: 10.1016/j.bbrc.2023.02.036

Experimental method

X-RAY DIFFRACTION (1.8 Å)