scholarly journals Deep time structural evolution of retroviral and filoviral surface envelope proteins

2021 ◽  
Author(s):  
Isidro Hotzel
Keyword(s):  
Envelope Protein ◽  
Ebola Virus ◽  
Structural Evolution ◽  
Structural Diversity ◽  
Protein Subunit ◽  
Deep Time ◽  
Host Interactions ◽  
Surface Envelope ◽  
Differential Expansion ◽  
Sandwich Core

The retroviral surface envelope protein subunit (SU) mediates receptor binding and triggers membrane fusion by the transmembrane subunit (TM). SU evolves rapidly under strong selective conditions, resulting in seemingly unrelated SU structures in highly divergent retroviruses. Structural modeling of the SU of several retroviruses and related endogenous retroviral elements with AlphaFold identifies a TM-proximal SU β-sandwich structure that has been conserved in the orthoretroviruses for at least 110 million years. The SU of orthoretroviruses diversified by differential expansion of the β-sandwich core to form domains involved in virus-host interactions. The β-sandwich domain is also conserved in the SU equivalent GP1 of Ebola virus although with a significantly different orientation in the trimeric envelope protein structure. The unified structural view of orthoretroviral SU and filoviral GP1 identifies an ancient, structurally conserved and evolvable domain underlying the structural diversity of orthoretroviral SU and filoviral GP1.

scholarly journals The Ebola Virus Glycoprotein: An Essential Envelope Protein for the Life Cycle of Ebola Virus

2015 ◽  
Vol 29 (S1) ◽  
Author(s):  
James Foresman ◽  
Bill Lackamp ◽  
Adrian McAfee ◽  
Marie Montague ◽  
Daniel Mungula ◽  
...  
Keyword(s):  
Life Cycle ◽  
Envelope Protein ◽  
Ebola Virus ◽  
Virus Glycoprotein

scholarly journals Structure of the Ebola Virus Envelope Protein MPER/TM Domain and its Interaction with the Fusion Loop Explains their Fusion Activity

2017 ◽  
Vol 112 (3) ◽  
pp. 78a
Author(s):  
Jinwoo Lee ◽  
David A. Nyenhuis ◽  
Elizabeth A. Nelson ◽  
David S. Cafiso ◽  
Judith M. White ◽  
...  
Keyword(s):  
Envelope Protein ◽  
Ebola Virus ◽  
Fusion Activity ◽  
Virus Envelope ◽  
Tm Domain ◽  
Virus Envelope Protein ◽  
Fusion Loop

scholarly journals Analyses of the core eukaryotic protein subunit of telomerase support extensive adaptation to different evolutionary and life histories in the Metazoa

2016 ◽  
Author(s):  
Alvina G. Lai ◽  
Natalia Pouchkina-Stantcheva ◽  
Alessia Di Donfrancesco ◽  
Gerda Kildisiute ◽  
Sounak Sahu ◽  
...  
Keyword(s):  
Alternative Splicing ◽  
Life Histories ◽  
Evolutionary History ◽  
Structural Evolution ◽  
Sequence Evolution ◽  
Dynamic Feature ◽  
Protein Subunit ◽  
Eukaryotic Protein ◽  
Telomere Biology ◽  
Splice Forms

AbstractMost animals employ telomerase, which consists of a catalytic subunit known as the telomerase reverse transcriptase (TERT) and an RNA template, to maintain telomere ends. Given the importance of TERT and the apparent importance of telomere biology in core metazoan life history traits like ageing and the control of somatic cell proliferation, we hypothesised that TERT would have patterns of sequence and regulatory evolution reflecting adaptations to diverse evolutionary and life histories across the Animal Kingdom. To test this, we performed a complete investigation of the evolutionary history of TERT across animals. We show that although TERT is almost ubiquitous across Metazoa, it has undergone substantial sequence evolution in canonical motifs. Beyond the known canonical motifs, we also identify and compare regions that are highly variable between lineages, but for which conservation exists within phyla. Recent data have highlighted the importance of alternate splice forms of TERT in non-canonical functions in some animals. Although animals may share some conserved introns, we find that the selection of exons for alternative splicing appears to be highly variable, and regulation by alternative splicing appears to be a very dynamic feature of TERT evolution. We show that even within a closely related group of triclad flatworms, where alternative splicing of TERT was previously correlated with reproductive strategy, we observe highly diverse alternative splicing patterns. Our work establishes that the evolutionary history and structural evolution of TERT involves previously unappreciated levels of change, supporting the view that this core eukaryotic protein has adapted to the requirements of diverse animal life histories.

Quorum Sensing Regulation as a Target for Antimicrobial Therapy

2021 ◽  
Vol 21 ◽  
Author(s):  
Caterine Henríquez Ruiz ◽  
Estefanie Osorio-Llanes ◽  
Mayra Hernández Trespalacios ◽  
Evelyn Mendoza-Torres ◽  
Wendy Rosales ◽  
...  
Keyword(s):  
Quorum Sensing ◽  
Molecular Mechanisms ◽  
Bacterial Resistance ◽  
Antimicrobial Agents ◽  
Bacterial Species ◽  
Cell Communication ◽  
Structural Evolution ◽  
Structural Diversity ◽  
Signal Molecules ◽  
Bacterial Survival

: Some bacterial species use a cell-to-cell communication mechanism called Quorum Sensing (QS). Bacteria release small diffusible molecules, usually termed signals which allow the activation of beneficial phenotypes that guarantee bacterial survival and the expression of a diversity of virulence genes in response to an increase in population density. The study of the molecular mechanisms that relate signal molecules with bacterial pathogenesis is an area of growing interest due to its use as a possible therapeutic alternative through the development of synthetic analogues of autoinducers as a strategy to regulate bacterial communication as well as the study of bacterial resistance phenomena, the study of these relationships is based on the structural diversity of natural or synthetic autoinducers and their ability to inhibit bacterial QS, which can be approached with a molecular perspective from the following topics: i) Molecular signals and their role in QS regulation; ii) Strategies in the modulation of Quorum Sensing; iii) Analysis of Bacterial QS circuit regulation strategies; iv) Structural evolution of natural and synthetic autoinducers as QS regulators. This mini-review allows a molecular view of the QS systems, showing a perspective on the importance of the molecular diversity of autoinducer analogs as a strategy for the design of new antimicrobial agents.

scholarly journals Envelope Glycoprotein Incorporation, Not Shedding of Surface Envelope Glycoprotein (gp120/SU), Is the Primary Determinant of SU Content of Purified Human Immunodeficiency Virus Type 1 and Simian Immunodeficiency Virus

2002 ◽  
Vol 76 (11) ◽  
pp. 5315-5325 ◽  
Author(s):  
Elena Chertova ◽  
Julian W. Bess, ◽  
Bruce J. Crise ◽  
Raymond C. Sowder ◽  
Terra M. Schaden ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Simian Immunodeficiency Virus ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Envelope Glycoprotein ◽  
Envelope Protein ◽  
Immunodeficiency Virus ◽  
Surface Envelope ◽  
Hiv 1

ABSTRACT Human immunodeficiency virus type 1 (HIV-1) and simian immunodeficiency virus (SIV) particles typically contain small amounts of the surface envelope protein (SU), and this is widely believed to be due to shedding of SU from mature virions. We purified proteins from HIV-1 and SIV isolates using procedures which allow quantitative measurements of viral protein content and determination of the ratios of gag- and env-encoded proteins in virions. All of the HIV-1 and most of the SIV isolates examined contained low levels of envelope proteins, with Gag:Env ratios of approximately 60:1. Based on an estimate of 1,200 to 2,500 Gag molecules per virion, this corresponds to an average of between 21 and 42 SU molecules, or between 7 and 14 trimers, per particle. In contrast, some SIV isolates contained levels of SU at least 10-fold greater than SU from HIV-1 isolates. Quantification of relative amounts of SU and transmembrane envelope protein (TM) provides a means to assess the impact of SU shedding on virion SU content, since such shedding would be expected to result in a molar excess of TM over SU on virions that had shed SU. With one exception, viruses with sufficient SU and TM to allow quantification were found to have approximately equivalent molar amounts of SU and TM. The quantity of SU associated with virions and the SU:TM ratios were not significantly changed during multiple freeze-thaw cycles or purification through sucrose gradients. Exposure of purified HIV-1 and SIV to temperatures of 55°C or greater for 1 h resulted in loss of most of the SU from the virus but retention of TM. Incubation of purified virus with soluble CD4 at 37°C resulted in no appreciable loss of SU from either SIV or HIV-1. These results indicate that the association of SU and TM on the purified virions studied is quite stable. These findings suggest that incorporation of SU-TM complexes into the viral membrane may be the primary factor determining the quantity of SU associated with SIV and HIV-1 virions, rather than shedding of SU from mature virions.

scholarly journals Role of the Mutation Q252R in Activating Membrane Fusion in the Murine Leukemia Virus Surface Envelope Protein

2003 ◽  
Vol 77 (20) ◽  
pp. 10841-10849 ◽  
Author(s):  
Chi-Wei Lu ◽  
Monica J. Roth
Keyword(s):  
Cell Fusion ◽  
Receptor Binding ◽  
Envelope Protein ◽  
Murine Leukemia Virus ◽  
Leukemia Virus ◽  
Host Cells ◽  
Cell Binding ◽  
Surface Envelope ◽  
Murine Leukemia ◽  
Cell Cell

ABSTRACT Entry of retroviruses into host cells requires the fusion between the viral and cellular membranes. It is unclear how receptor binding induces conformational changes within the surface envelope protein (SU) that activate the fusion machinery residing in the transmembrane envelope protein (TM). In this report, we have isolated a point mutation, Q252R, within the proline-rich region of the 4070A murine leukemia virus SU that altered the virus-cell binding characteristics and induced cell-cell fusion. Q252R displays a SU shedding-sensitive phenotype. Cell-cell fusion is receptor dependent and is observed only in the presence of MuLV Gag-Pol. Both cellular binding and fusion by Q252R are greatly enhanced in conjunction of G100R, a mutation within the SU variable region A which increases viral binding through an independent mechanism. Deletion of a conserved histidine (His36) at the SU N terminus abolished cell-cell fusion by G100R/Q252R Env without compromising virus-cell binding. Although G100R/Q252R virus has no detectable titer, replacement of the N-terminal nine 4070A SU amino acids with the equivalent ecotropic MuLV sequence restored viral infectivity. These studies provide insights into the functional cooperation between multiple elements of SU required to signal receptor binding and activate the fusion machinery.

Promising agents at the interface of biology and oncology derived through chemical synthesis

2007 ◽  
Vol 79 (12) ◽  
pp. 2189-2216 ◽  
Author(s):  
Rebecca M. Wilson ◽  
Samuel J. Danishefsky
Keyword(s):  
Chemical Synthesis ◽  
Natural Product ◽  
Prostate Specific Antigen ◽  
Research Program ◽  
Envelope Protein ◽  
Specific Antigen ◽  
Biologically Relevant ◽  
The Past ◽  
Surface Envelope

This account traces the development of our synthetic glycopeptide- and glycoprotein-based research program over the past decade. We recount the syntheses of a number of biologically relevant, natural product-inspired glycopeptide constructs, including those associated with prostate specific antigen (PSA) and with the gp120 surface envelope protein of HIV. We also describe our progress toward the synthesis of the multiply glycosylated protein, erythropoietin (EPO). Particular emphasis is placed on the development of enabling methodologies which allow for the ligation of complex glycopeptide fragments, thus rendering it possible to access, through purely synthetic means, homogeneous, multidomainal glycopeptide and glycoprotein constructs.

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