5B56

Crystal structure of HIV-1 VPR C-Terminal domain and DIBB-M-Importin-Alpha2 complex

Summary for 5B56

• Entry DOI: 10.2210/pdb5b56/pdb
• Related: 3WPT
• Descriptor: Importin subunit alpha-1, Protein Vpr (3 entities in total)
• Functional Keywords: arm repeat, all alpha protein, nuclear import, importin-beta, nls-cargo, protein transport-viral protein complex, protein transport/viral protein
• Biological source: Mus musculus (Mouse); More
• Total number of polymer chains: 6
• Total formula weight: 105343.37

Authors

Miyatake, H.,Sanjoh, A.,Matusda, G.,Murakami, T.,Murakami, H.,Hagiwara, K.,Yokoyama, M.,Sato, H.,Miyamoto, Y.,Dohmae, N.,Aida, Y. (deposition date: 2016-04-25, release date: 2016-06-01, Last modification date: 2023-11-08)

Primary citation

Miyatake, H.,Sanjoh, A.,Murakami, T.,Murakami, H.,Matsuda, G.,Hagiwara, K.,Yokoyama, M.,Sato, H.,Miyamoto, Y.,Dohmae, N.,Aida, Y.
Molecular Mechanism of HIV-1 Vpr for Binding to Importin-alpha
J.Mol.Biol., 428:2744-2757, 2016

PubMed Abstract: Viral protein R (Vpr) is an accessory gene product of human immunodeficiency virus type 1 (HIV-1) that plays multiple important roles associated with viral replication. Structural studies using NMR have revealed that Vpr consists of three α-helices and contains flexible N- and C-termini. However, the molecular mechanisms associated with Vpr function have not been elucidated. To investigate Vpr multifunctionality, we performed an X-ray crystallographic study of Vpr complexes containing importin-α, a known Vpr binding partner present in host cells. Elucidation of the crystal structure revealed that the flexible C-terminus changes its conformation to a twisted β-turn via an induced-fit mechanism, enabling binding to a minor nuclear localization signal (NLS) site of importin-α. The Vpr C-terminus can also bind with major NLS sites of importin-α in an extended conformation in different ways. These results, which represent the first reported crystallographic analysis of Vpr, demonstrate the multifunctional aspects that enable Vpr interaction with a variety of cellular proteins.

PubMed: 27181198
DOI: 10.1016/j.jmb.2016.05.003

Experimental method

X-RAY DIFFRACTION (2.3 Å)