Solid-State NMR Spectroscopy of Human Immunodeficiency Virus Fusion Peptides Associated with Host-Cell-Like Membranes: 2D Correlation Spectra and Distance Measurements Support a Fully Extended Conformation and Models for Specific Antiparallel Strand Registries

Wang, Qiang; Bodner, Michele L.; Weliky, David P.

doi:10.1021/ja077302m

Cited by 55 publications

(189 citation statements)

References 97 publications

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“…In the present HFP study, the membranes contained Ϸ30 mol% cholesterol which correlated with the Ϸ30 and Ϸ45 mol% cholesterol in membranes of host cells of HIV and in membranes of HIV, respectively (13). In this composition, solid-state NMR data supported a fully extended ␤ sheet conformation for the Ala-1 to Gly-16 region of HFPmn with crossing of adjacent hydrogen bonded HFPmns near Phe-8 and Leu-9 (14).…”

supporting

confidence: 66%

“…3 shows experimentally-based membrane insertion models for HFPmn_mut, HFPmn, and HFPtr in antiparallel ␤ sheet structure. The ␤ strand conformation was supported by the 13 CO peak chemical shifts for the labeled residues (Table S1) and the antiparallel ␤ sheet structures for HFPmn and HFPtr were based on previous experiments (14,20). The depths of insertion follow the trend that HFPmn_mut Ͻ HFPmn Ͻ HFPtr.…”

Section: Co-(5-19 F) Redor Confirms the Hfpmn Membrane Locationmentioning

confidence: 90%

“…In addition, 13 13 COs whose signals would overlap with the HFP 13 CO signals. Use of ether-linked rather than ester-linked lipids does not affect HFP structure (14).…”

mentioning

confidence: 93%

“…The strands are in antiparallel ␤ sheet structure with adjacent strand crossing near Phe-8 and Leu-9. This is the known structure for a large fraction of HFPmn peptides (14). The number of strands in a sheet is not known but is likely a small number (19).…”

mentioning

confidence: 99%

“…The 31 P and 16-19 F lipid nuclei are respectively located near the surface and the center of the membrane. The analysis of membrane location assumes that all of the constructs have the known HFPmn structure in which the Ala-1 to Gly-16 region is fully extended and a large fraction of HFPs assemble into an antiparallel ␤ sheet structure with adjacent strand crossing near Phe-8 and Leu-9 (14). The ␤ sheet structure is supported by the similar 13 CO shifts for a given residue among the different constructs (Table S1).…”

mentioning

confidence: 99%

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A strong correlation between fusogenicity and membrane insertion depth of the HIV fusion peptide

Wang

Sun

Weliky³

2009

Proc. Natl. Acad. Sci. U.S.A.

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Fusion between the membrane of HIV and the membrane of a host cell is a crucial step in HIV infection and is catalyzed by the binding of the fusion peptide domain (HFP) of the HIV gp41 protein to the host cell membrane. The HFP by itself induces vesicle fusion and is a useful model system to understand the fusion peptide/host cell membrane interaction. This article reports an experimental correlation between the membrane locations of different HFP constructs and their fusogenicities. The constructs were the HFP monomer with Val-2 to Glu-2 mutation (HFPmn_mut), wild type HFP monomer (HFPmn), and wild type HFP trimer (HFPtr). All constructs have predominant ␤ sheet structure in membranes with physiologically relevant cholesterol content. HFPmn_mut does not fuse vesicles, HFPmn has moderate fusion rate, and HFPtr has the putative oligomerization state of HIV gp41 and a very rapid fusion rate. The HFP membrane locations were probed with solid-state NMR measurements of distances between labeled carbonyl ( 13 CO) nuclei in the HFP backbone and lipid nuclei in the surface or interior regions of the membrane bilayer. HFPmn_mut is located at the membrane surface, HFPmn is inserted into a single membrane leaflet, and HFPtr is the most deeply inserted construct with contact with the center of the membrane. These results show a clear positive correlation between the insertion depths and the fusion activities of the HFP constructs. Other disease-causing enveloped viruses contain fusion peptides and this correlation may be a general structure-function model for these peptides.L ike many viruses that cause human disease, HIV is enveloped by a membrane obtained during virus budding from a previously infected host cell and infection of a new cell requires fusion between the viral membrane and the cell membrane. Fusion is catalyzed by the HIV fusion protein gp41, which has Ϸ170 ectodomain residues outside the virus including a Ϸ20-residue N-terminal fusion peptide (HFP) that binds to target cell membranes (1). Studies of HIV with a truncated or mutated HFP showed that the HFP is crucial in the fusion process (2, 3). Functionally critical fusion peptides are also found in fusion proteins of other enveloped viruses such as influenza and Ebola (1). Chemically synthesized peptides with HFP sequences have been developed as fusion model systems and provide information about HFP perturbation of target membranes. Free HFPs induce vesicle fusion and there are strong correlations between the mutation/activity relationships of HFP-induced fusion and HIV/host cell fusion (3).There have been some number of HFP structural studies, but in our view, there have not yet been clear correlations between HFP structure and fusogenic function. For example, membraneassociated HFP can adopt either helical or ␤ strand conformation and there has been effort to determine a correlation between conformation and fusogenicity. However, this work has resulted in conflicting models such as: (i) the helical conformation is fusogenic and the ␤ strand conformation i...

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supporting

confidence: 66%

Section: Co-(5-19 F) Redor Confirms the Hfpmn Membrane Locationmentioning

confidence: 90%

“…In addition, 13 13 COs whose signals would overlap with the HFP 13 CO signals. Use of ether-linked rather than ester-linked lipids does not affect HFP structure (14).…”

mentioning

confidence: 93%

mentioning

confidence: 99%

mentioning

confidence: 99%

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A strong correlation between fusogenicity and membrane insertion depth of the HIV fusion peptide

Wang

Sun

Weliky³

2009

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

106

147

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Dynamic Transitions of Membrane-Active Peptides

Grage

Afonin

Ulrich

2009

Methods in Molecular Biology

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Membrane-active peptides or protein segments play an important role in many biological processes at the cellular interface to the environment. They are involved, e.g., in cellular fusion or host defense, where they can cause not only merging but also the destabilization of cell membranes. Many factors determine how these typically amphipathic peptides interact with the lipid bilayer. For example, the peptide orientation in the membrane determines which parts of the peptide are exposed to the hydrophobic bilayer interior or to the polar lipid/water interface. As another example, oligomerization is required for many activities such as pore formation. Peptides have been often classified according to a single characteristic mode of interaction with the bilayer, but over the years a more versatile picture has emerged. It appears that any single peptide can adopt several different alignments and/or oligomeric states in response to changes in the environment. For instance, many antimicrobial peptides adopt a surface-parallel alignment at low concentration, but they tilt obliquely into or even fully insert transmembrane into the bilayer above a critical peptide-to-lipid ratio, often in the form of oligomeric pores. Similar changes in peptide orientation or oligomeric state have been observed as a function of, e.g., temperature, lipid composition, pH, or induced by a synergistic partner peptide. Such transitions between peptide states can be regarded as the result of a re-adjustment in the balance between peptide-peptide and peptide-lipid interactions, as the environment conditions are changed. Though often studied in model membrane systems, such rich variety of peptide states is even more likely to occur in native biomembranes with their diverse compositions and physicochemical properties. The ability to undergo transitions between different states thus plays a fundamental role for the biological activities of membrane-active peptides.

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Membrane Composition Modulates Fusion by Altering Membrane Properties and Fusion Peptide Structure

Meher

Chakraborty

2019

J Membrane Biol

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Membrane fusion, one of the most essential processes in the life of eukaryotes, occurs when two separate lipid bilayers merge into a continuous bilayer and internal contents of two separated membranes mingle. There is a certain class of proteins that assist the binding of the viral envelope to the target host cell and catalyzing fusion. All class I viral fusion proteins contain a highly conserved 20-25 amino-acid amphipathic peptide at the N-terminus, which is essential for fusion activity and is termed as the 'fusion peptide'. It has been shown that insertion of fusion peptides into the host membrane and the perturbation in the membrane generated thereby is crucial for membrane fusion. Significant efforts have been given in the last couple of decades to understand the lipid-dependence of structure and function of the fusion peptide in membranes to understand the role of lipid compositions in membrane fusion. In addition, the lipid compositions further change the membrane physical properties and alter the mechanism and extent of membrane fusion. Therefore, lipid compositions modulate membrane fusion by changing membrane physical properties and altering structure of the fusion peptide.Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

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Solid-State NMR Spectroscopy of Human Immunodeficiency Virus Fusion Peptides Associated with Host-Cell-Like Membranes: 2D Correlation Spectra and Distance Measurements Support a Fully Extended Conformation and Models for Specific Antiparallel Strand Registries

Cited by 55 publications

References 97 publications

A strong correlation between fusogenicity and membrane insertion depth of the HIV fusion peptide

A strong correlation between fusogenicity and membrane insertion depth of the HIV fusion peptide

Dynamic Transitions of Membrane-Active Peptides

Membrane Composition Modulates Fusion by Altering Membrane Properties and Fusion Peptide Structure

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