scholarly journals Design of a novel tryptophan-rich membrane-active antimicrobial peptide from the membrane-proximal region of the HIV glycoprotein, gp41

2012 ◽  
Vol 8 ◽  
pp. 1172-1184 ◽  
Author(s):  
Evan F Haney ◽  
Leonard T Nguyen ◽  
David J Schibli ◽  
Hans J Vogel
Keyword(s):  
Antimicrobial Peptide ◽  
Positive Charge ◽  
Helical Structure ◽  
Physicochemical Characteristics ◽  
Proximal Region ◽  
Peptide Sequence ◽  
Interfacial Region ◽  
Cytotoxic Activities ◽  
Glycoprotein Gp41 ◽  
Membrane Proximal Region

A number of physicochemical characteristics have been described which contribute to the biological activity of antimicrobial peptides. This information was used to design a novel antimicrobial peptide sequence by using an intrinsically inactive membrane-associated peptide derived from the HIV glycoprotein, gp41, as a starting scaffold. This peptide corresponds to the tryptophan-rich membrane-proximal region of gp41, which is known to interact at the interfacial region of the viral membrane and adopts a helical structure in the presence of lipids. Three synthetic peptides were designed to increase the net positive charge and amphipathicity of this 19-residue peptide. Ultimately, the peptide with the greatest degree of amphipathicity and largest positive charge proved to be the most potent antimicrobial, and this peptide could be further modified to improve the antimicrobial activity. However, the other two peptides were relatively ineffective antimicrobials and instead proved to be extremely hemolytic. This work demonstrates a novel approach for the design of unexplored antimicrobial peptide sequences but it also reveals that the biological and cytotoxic activities of these polypeptides depend on a number of interrelated factors.

Herpes simplex virus glycoprotein B (gB) mutations define structural sites in domain I, the membrane proximal region, and the cytodomain that regulate entry.

2021 ◽  
Author(s):  
Qing Fan ◽  
Richard Longnecker ◽  
Sarah A. Connolly
Keyword(s):  
Cell Fusion ◽  
Virus Entry ◽  
Proximal Region ◽  
Glycoprotein B ◽  
Viral Fusion ◽  
Viral Fusion Protein ◽  
Membrane Proximal Region ◽  
Domain V ◽  
Domain I ◽  
Cell Cell

The viral fusion protein glycoprotein B (gB) is conserved in all herpesviruses and is essential for virus entry. During entry, gB fuses viral and host cell membranes by refolding from a prefusion to a postfusion form. We previously introduced three structure-based mutations (gB-I671A/H681A/F683A) into the domain V arm of the gB ectodomain that resulted in reduced cell-cell fusion. A virus carrying these three mutations (called gB3A) displayed a small plaque phenotype and remarkably delayed entry into cells. To identify mutations that could counteract this phenotype, we serially passaged the gB3A virus and selected for revertant viruses with increased plaque size. Genomic sequencing revealed that the revertant viruses had second-site mutations in gB, including E187A, M742T, and S383F/G645R/V705I/V880G. Using expression constructs encoding these mutations, only gB-V880G was shown to enhance cell-cell fusion. In contrast, all of the revertant viruses showed enhanced entry kinetics, underscoring the fact that cell-cell fusion and virus-cell fusion are different. The results indicate that mutations in three different regions of gB (domain I, the membrane proximal region, and the cytoplasmic tail domain) can counteract the slow entry phenotype of gB3A virus. Mapping these compensatory mutations to prefusion and postfusion structural models suggests sites of intramolecular functional interactions with the gB domain V arm that may contribute to the gB fusion function. Importance The nine human herpesviruses are ubiquitous and cause a range of disease in humans. Glycoprotein B (gB) is an essential viral fusion protein that is conserved in all herpesviruses. During host cell entry, gB mediates virus-cell membrane fusion by undergoing a conformational change. Structural models for the prefusion and postfusion form of gB exist, but the details of how the protein converts from one to the other are unclear. We previously introduced structure-based mutations into gB that inhibited virus entry and fusion. By passaging this entry-deficient virus over time, we selected second-site mutations that partially restore virus entry. The location of these mutations suggest regulatory sites that contribute to fusion and gB refolding during entry. gB is a target of neutralizing antibodies and defining how gB refolds during entry could provide a basis for the development of fusion inhibitors for future research or clinical use.

scholarly journals Identification of Antimicrobial Peptides from the Microalgae Tetraselmis suecica (Kylin) Butcher and Bactericidal Activity Improvement

Marine Drugs ◽  
2019 ◽  
Vol 17 (8) ◽  
pp. 453 ◽  
Author(s):  
Guzmán ◽  
Wong ◽  
Román ◽  
Cárdenas ◽  
Alvárez ◽  
...  
Keyword(s):  
Antibacterial Activity ◽  
Pathogenic Bacteria ◽  
Bioactive Peptides ◽  
De Novo ◽  
Helical Structure ◽  
Antimicrobial Activities ◽  
Peptide Sequence ◽  
Tetraselmis Suecica ◽  
Defense Strategies ◽  
Key Residues

The outburst of microbial resistance to antibiotics creates the need for new sources of active compounds for the treatment of pathogenic microorganisms. Marine microalgae are of particular interest in this context because they have developed tolerance and defense strategies to resist the exposure to pathogenic bacteria, viruses, and fungi in the aquatic environment. Although antimicrobial activities have been reported for some microalgae, natural algal bioactive peptides have not been described yet. In this work, acid extracts from the microalga Tetraselmis suecica with antibacterial activity were analyzed, and de novo sequences of peptides were determined. Synthetic peptides and their alanine and lysine analogs allowed identifying key residues and increasing their antibacterial activity. Additionally, it was determined that the localization of positive charges within the peptide sequence influences the secondary structure with tendency to form an alpha helical structure.

scholarly journals Ligand-specific utilization of the extracellular membrane-proximal region of the gp130-related signalling receptors

1999 ◽  
Vol 345 (1) ◽  
pp. 25-32 ◽  
Author(s):  
Annet HAMMACHER ◽  
John WIJDENES ◽  
Douglas J. HILTON ◽  
Nicos A. NICOLA ◽  
Richard J. SIMPSON ◽  
...  
Keyword(s):  
Proximal Region ◽  
Leukaemia Inhibitory Factor ◽  
Binding Affinities ◽  
Wild Type ◽  
Correct Orientation ◽  
Fibronectin Type Iii ◽  
Membrane Proximal Region ◽  
Stimulating Factor ◽  
Fibronectin Type

The receptor gp130 is used by the interleukin-6 (IL-6)-type cytokines, which include IL-6 and leukaemia-inhibitory factor (LIF). To investigate the role of the three extracellular membrane-proximal fibronectin-type-III-like (FNIII) modules of gp130 and the related receptor for granulocyte colony-stimulating factor (G-CSFR) in cytokine signal transduction we have transfected into murine myeloid M1-UR21 cells the chimaera (GR-FNIII)gp130, which contains the membrane-proximal FNIII modules of the G-CSFR on a gp130 backbone, and its complement, the chimaera (gp130-FNIII)GR. Whereas the binding affinities of 125I-labelled IL-6 to (GR-FNIII)gp130, or of 125I-Tyr1,3-G-CSF to (gp130-FNIII)GR, were similar to wild-type gp130 and wild-type G-CSFR, respectively, 125I-LIF failed to bind with high affinity to (GR-FNIII)gp130. In assays measuring differentiation the (gp130-FNIII)GR cells were fully responsive to G-CSF, whereas the (GR-FNIII)gp130 cells responded fully to the agonistic anti-gp130 monoclonal antibody (mAb) B-S12, but not to IL-6 or LIF. Neutralizing mAbs that recognize the membrane-proximal FNIII modules of gp130 or the G-CSFR differentially interfered with signalling by B-S12, LIF and G-CSF. The data suggest that B-S12 and G-CSF induce the correct orientation or conformation for signalling by the wild-type and chimaeric homodimeric receptors, that the membrane-proximal region of gp130 is important for the correct formation of the signalling IL-6-IL-6 receptor-gp130 complex and that this region is also involved in LIF-dependent receptor heterodimerization and signalling.

Characterisation of helical structure in AFM micrographs of a trimer of the peptide sequence (ValGlyGlyValGly)

2014 ◽  
Vol 46 (10-11) ◽  
pp. 679-682 ◽  
Author(s):  
James Eric Castle ◽  
Neluta Ibris ◽  
Anna Maria Salvi ◽  
Pasquale Moscarelli ◽  
Brigida Bochicchio ◽  
...  
Keyword(s):  
Helical Structure ◽  
Peptide Sequence ◽  
Afm Micrographs

Domain-Specific Interactions of Talin with the Membrane-Proximal Region of the Integrin β3 Subunit†

Biochemistry ◽  
2003 ◽  
Vol 42 (27) ◽  
pp. 8307-8312 ◽  
Author(s):  
Tobias S. Ulmer ◽  
David A. Calderwood ◽  
Mark H. Ginsberg ◽  
Iain D. Campbell
Keyword(s):  
Proximal Region ◽  
Specific Interactions ◽  
Domain Specific ◽  
Integrin Β3 ◽  
Membrane Proximal Region
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