Chemical Synthesis and Single Channel Properties of Tetrameric and Pentameric TASPs (Template-assembled Synthetic Proteins) Derived from the Transmembrane Domain of HIV Virus Protein u (Vpu)

Becker, Christian F. W.; Oblatt-Montal, M.; Kochendoerfer, Gerd G.; Montal, Mauricio

doi:10.1074/jbc.m313212200

Cited by 51 publications

(40 citation statements)

References 38 publications

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“…This is consistent with the molecular modeling studies performed by several groups (38)(39)(40)(41)(42). Chemically tethered tetramers and pentamers of the Vpu TM domain have been shown to form ion channels with a conductance similar to that of the native protein (91). The NMR data presented here may reflect the structure of Vpu(1-40) within an oligomeric channel, although we do not have direct evidence of ion channel activity in our samples.…”

Section: A Structural Model For Vpusupporting

confidence: 92%

Structure and Dynamics of the HIV-1 Vpu Transmembrane Domain Revealed by Solid-State NMR with Magic-Angle Spinning

2005

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We report solid-state nuclear magnetic resonance (NMR) measurements on the peptide Vpu(1-40), comprising residues 1-40 of the 81-residue type 1 integral membrane protein Vpu encoded by the HIV-1 genome. On the basis of a combination of 13C and 15N NMR chemical shifts under magic-angle spinning (MAS), effects of local mobility on NMR signal intensities, site-specific MAS NMR line widths, and NMR-detected hydrogen-deuterium exchange, we develop a model for the structure and dynamics of the Vpu(1-40) monomer in phospholipid bilayer membranes. Our data are largely consistent with earlier structural studies of Vpu peptides by Opella and co-workers, in which solution NMR and solid-state NMR without MAS were used, but our data provide new information about local variations in the degree of mobility and structural order. In addition, our data indicate that the transmembrane alpha-helix of Vpu(1-40) extends beyond the hydrophobic core of the bilayer. We find no evidence for heterogeneity in the conformation and intermolecular contacts of the transmembrane alpha-helix, with the exception of two distinct chemical shifts observed for the C alpha and C beta atoms of A18 that may reflect distinct modes of helix-helix interaction. These results have possible implications for the supramolecular structure of Vpu oligomers that form cation-selective ion channels.

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Section: A Structural Model For Vpusupporting

confidence: 92%

Structure and Dynamics of the HIV-1 Vpu Transmembrane Domain Revealed by Solid-State NMR with Magic-Angle Spinning

2005

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“…Comparable stability for structurally diverse oligomers in bilayers may explain experimental observations of multiple conductance levels for Vpu ion channels. 1,10,[13][14][15] Given that a variety of Vpu 1-40 oligomer structures coexist in DOPC/DOPG bilayers, we can not analyze our solid-state NMR data unequivocally in terms of a single structure. However, the fact that 2D 13 C-13 C spectra of Vpu in bilayers show a single set of 13 C chemical shifts 17 suggests that peptide conformations and intermolecular interactions in the predominant oligomers are similar.…”

Section: Discussionmentioning

confidence: 99%

“…9 The second function depends principally on the single transmembrane TM segment of Vpu, contained within residues 1-30, as sequence alterations in the TM segment have been shown to interfere with this function. 2 Full-length Vpu and various N-terminal peptides containing the TM segment have been shown to form cation-selective channels in model membranes 1,[10][11][12][13][14][15] and in cells. 12 These ion channels presumably form by association of a-helical TM segments into homo-oligomeric bundles, with ions passing through the central pore of the helix bundle.…”

Section: Introductionmentioning

confidence: 99%

Oligomerization state and supramolecular structure of the HIV‐1 Vpu protein transmembrane segment in phospholipid bilayers

et al. 2010

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HIV-1 Vpu is an 81-residue protein with a single N-terminal transmembrane (TM) helical segment that is involved in the release of new virions from host cell membranes. Vpu and its TM segment form ion channels in phospholipid bilayers, presumably by oligomerization of TM helices into a pore-like structure. We describe measurements that provide new constraints on the oligomerization state and supramolecular structure of residues 1-40 of Vpu (Vpu 1-40 ), including analytical ultracentrifugation measurements to investigate oligomerization in detergent micelles, photo-induced crosslinking experiments to investigate oligomerization in bilayers, and solid-state nuclear magnetic resonance measurements to obtain constraints on intermolecular contacts between and orientations of TM helices in bilayers. From these data, we develop molecular models for Vpu TM oligomers. The data indicate that a variety of oligomers coexist in phospholipid bilayers, so that a unique supramolecular structure can not be defined. Nonetheless, since oligomers of various sizes have similar intermolecular contacts and orientations, molecular models developed from our data are most likely representative of Vpu TM oligomers that exist in host cell membranes.

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“…e NMR solution structure of the cytoplasmic domain of Vpu in aqueous solution (1VPU). Ten representative members of the conformational ensemble are shown by ribbons of different color [466,[478][479][480][483][484][485][486]. Based on the comprehensive biophysical analysis of the Vpu 1-40 domain by analytical ultracentrifugation to investigate oligomerization in detergent micelles, photo-induced crosslinking to investigate oligomerization in bilayers and solid-state nuclear magnetic resonance to obtain constraints on intermolecular contacts between and orientations of TM helices in bilayers, the molecular models for the Vpu TM oligomers were developed [487].…”

Section: Vpumentioning

confidence: 99%

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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Chemical Synthesis and Single Channel Properties of Tetrameric and Pentameric TASPs (Template-assembled Synthetic Proteins) Derived from the Transmembrane Domain of HIV Virus Protein u (Vpu)

Cited by 51 publications

References 38 publications

Structure and Dynamics of the HIV-1 Vpu Transmembrane Domain Revealed by Solid-State NMR with Magic-Angle Spinning

Structure and Dynamics of the HIV-1 Vpu Transmembrane Domain Revealed by Solid-State NMR with Magic-Angle Spinning

Oligomerization state and supramolecular structure of the HIV‐1 Vpu protein transmembrane segment in phospholipid bilayers

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

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