HIV-1 encoded virus protein U (Vpu) solution structure of the 41–62 hydrophilic region containing the phosphorylated sites Ser52 and Ser56

Coadou, Gaël; Evrard‐Todeschi, Nathalie; Gharbi-Benarous, Josyane; Bénarous, Richard; Girault, J. P.

doi:10.1016/s0141-8130(01)00184-2

Cited by 29 publications

(29 citation statements)

References 36 publications

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“…(d) Part of the backbone (37-69) of the Vpu cytoplasmic domain (37-81) structure (18). (e) Backbone (41-62) of the minimum energy-minimized conformer of the free P-Vpu 41-62 peptide at pH 7.2. to the Vpu protein) were investigated in phosphate-buffered solution, using NMR and molecular modeling simulation (17). Simulations, in accordance with NMR experiments, showed that the P-Vpu 41-62 phosphorylated peptide analogue ( Figure 1e) has different structural features than the parent Vpu 41-62 peptide ( Figure 1d) (18).…”

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confidence: 75%

“…Then they are required for binding of Vpu to -TrCP to promote CD4 degradation (13). The structure of the free P-Vpu 41-62 phosphorylated peptide by NMR spectroscopy and restrained molecular dynamics shows that the peptide adopts in solution (Figure 1e) a helical N-terminal part, a bend including the phosphorylation motif DpS 52 GNEpS 56 , and a flexible extended "tail" for the C-terminal part (17).…”

Section: Discussionmentioning

confidence: 99%

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NMR Studies of the Phosphorylation Motif of the HIV-1 Protein Vpu Bound to the F-Box Protein β-TrCP

et al. 2003

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A protein-protein association regulated by phosphorylation of serine is examined by NMR studies. Degradation of the HIV receptor CD4 by the proteasome, mediated by the HIV-1 protein Vpu, is crucial for the release of fully infectious virions. Phosphorylation of Vpu at two sites, Ser52 and Ser56, on the motif DSGXXS is required for the interaction of Vpu with the ubiquitin ligase SCF-betaTrCP which triggers CD4 degradation by the proteasome. This motif is conserved in several signaling proteins known to be degraded by the proteasome. To elucidate the basis of beta-TrCP recognition, the bound conformation of the P-Vpu(41-62) peptide was determined by using NMR and MD. The TRNOE intensities provided distance constraints which were used in simulated annealing. The beta-TrCP-bound structure of P-Vpu was found to be similar to the structure of the free peptide in solution and to the structure recognized by its antibody. Residues 50-57 formed a bend while the phosphate groups are pointing away. The binding fragment was studied by STD-NMR spectroscopy. The phosphorylated motif DpS(52)GNEpS(56) was found to make intimate contact with beta-TrCP, and pSer52 displays the strongest binding effect. It is suggested that Ser phosphorylation allows protein-protein association by electrostatic stabilization: an obvious negative binding region of Vpu was recognizable by positive residues (Arg and Lys) of the WD domain of beta-TrCP. The Ile46 residue was also found essential for interaction with the beta-TrCP protein. Leu45 and Ile46 side chains lie in close proximity to a hydrophobic pocket of the WD domain.

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confidence: 75%

Section: Discussionmentioning

confidence: 99%

NMR Studies of the Phosphorylation Motif of the HIV-1 Protein Vpu Bound to the F-Box Protein β-TrCP

et al. 2003

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“…NMR studies performed on Vpu 39–81 in DPC micelles (67) and Vpu 27–57 in mechanically aligned POPC bilayers (68) suggest that phosphorylation causes no drastic structural change in Vpu except an elongation of helix-3, reduction in helicity at helix-2 and reduction in mobility of the loop-2 region in micelles. While both NMR and MD simulation performed by Girault et al (69–71) show that loop-2 becomes structured and helix-3 becomes unstructured upon phosphorylation. The lowest energy structure of VpuFull shows that S56 faces toward to the aqueous solution and S52 faces down to the lipid surface, and loop-2 roughly lies on the membrane, which might suggest that S56 is easier to be phosphorylated by CK2.…”

Section: Discussionmentioning

confidence: 97%

Structural determination of virus protein U from HIV-1 by NMR in membrane environments

Zhang

Lin

Das

et al. 2015

Biochimica et Biophysica Acta (BBA) - Biomembranes

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Virus protein U (Vpu) from HIV-1, a small membrane protein composed of a transmembrane helical domain and two α-helices in an amphipathic cytoplasmic domain, down modulates several cellular proteins, including CD4, BST-2/CD317/tetherin, NTB-A, and CCR7. The interactions of Vpu with these proteins interfere with the immune system and enhance the release of newly synthesized virus particles. It is essential to characterize the structure and dynamics of Vpu in order to understand the mechanisms of the protein-protein interactions, and potentially to discover antiviral drugs. In this article, we describe investigations of the cytoplasmic domain of Vpu as well as full-length Vpu by NMR spectroscopy. These studies are complementary to earlier analysis of the transmembrane domain of Vpu. The results suggest that the two helices in the cytoplasmic domain form a U-shape. The length of the inter-helical loop in the cytoplasmic domain and the orientation of the third helix vary with the lipid composition, which demonstrate that the C-terminal helix is relatively flexible, providing accessibility for interaction partners.

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“…Solution NMR analysis of Vpu in the presence of DHPC micelles showed evidence of helical regions from residues 28-50 and 58-70 [480]. Finally, solution NMR studies revealed that the Vpu (41-62) structure in an aqueous solution depends on phosphorylation of S52 and S56 [491,492]. Figure 19f shows that, in agreement with experimental data, the cytoplasmic domain of HIV-1 Vpu is predicted to be highly disordered and is expected to have an a-MoRF.…”

Section: Vpumentioning

confidence: 95%

Protein intrinsic disorder as a flexible armor and a weapon of HIV-1

Xue

Mizianty

Kurgan

et al. 2011

Cell. Mol. Life Sci.

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Many proteins and protein regions are disordered in their native, biologically active states. These proteins/regions are abundant in different organisms and carry out important biological functions that complement the functional repertoire of ordered proteins. Viruses, with their highly compact genomes, small proteomes, and high adaptability for fast change in their biological and physical environment utilize many of the advantages of intrinsic disorder. In fact, viral proteins are generally rich in intrinsic disorder, and intrinsically disordered regions are commonly used by viruses to invade the host organisms, to hijack various host systems, and to help viruses in accommodation to their hostile habitats and to manage their economic usage of genetic material. In this review, we focus on the structural peculiarities of HIV-1 proteins, on the abundance of intrinsic disorder in viral proteins, and on the role of intrinsic disorder in their functions.

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HIV-1 encoded virus protein U (Vpu) solution structure of the 41–62 hydrophilic region containing the phosphorylated sites Ser52 and Ser56

Cited by 29 publications

References 36 publications

NMR Studies of the Phosphorylation Motif of the HIV-1 Protein Vpu Bound to the F-Box Protein β-TrCP

NMR Studies of the Phosphorylation Motif of the HIV-1 Protein Vpu Bound to the F-Box Protein β-TrCP

Structural determination of virus protein U from HIV-1 by NMR in membrane environments

Protein intrinsic disorder as a flexible armor and a weapon of HIV-1

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