Molecular basis of endosomal-membrane association for the dengue virus envelope protein

Rogers, David; Kent, Michael S.; Rempe, Susan

doi:10.1016/j.bbamem.2014.12.018

Cited by 19 publications

(20 citation statements)

References 102 publications

(134 reference statements)

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“…The ΔG* u per trimer measured here of 20 kcal/mol (20% PG) is more than sufficient to support membrane fusion, as 3-5 trimers likely bind simultaneously to the host membrane and the bending free energy required to form the fusion stalk is estimated to be 22-30 kcal/mol (61). Prior work demonstrated that fusion of Dengue virus with endosomal membranes occurs in late endosomes, where the concentration of negatively-charged lipids is high.…”

Section: Resultsmentioning

confidence: 89%

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Method for measuring the unbinding energy of strongly-bound membrane-associated proteins

Bauve

Vernon

et al. 2016

Biochimica et Biophysica Acta (BBA) - Biomembranes

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We describe a new method to measure the activation energy for unbinding (enthalpy ΔH*u and free energy ΔG*u) of a strongly-bound membrane-associated protein from a lipid membrane. It is based on measuring the rate of release of a liposome-bound protein during centrifugation on a sucrose gradient as a function of time and temperature. The method is used to determine ΔH*u and ΔG*u for the soluble dengue virus envelope protein (sE) strongly bound to 80:20 POPC:POPG liposomes at pH 5.5. ΔH*u is determined from the Arrhenius equation whereas ΔG*u is determined by fitting the data to a model based on mean first passage time for escape from a potential well. The binding free energy ΔGb of sE was also measured at the same pH for the initial, predominantly reversible, phase of binding to a 70:30 PC:PG lipid bilayer. The unbinding free energy (20 +/− 3 kcal/mol, 20% PG) was found to be roughly three times the binding energy per monomer, (7.8 +/− 0.3 kcal/mol for 30% PG, or est. 7.0 kcal/mol for 20% PG). This is consistent with data showing that free sE is a monomer at pH 5.5, but assembles into trimers after associating with membranes. This new method to determine unbinding energies should be useful to understand better the complex interactions of integral monotopic proteins and strongly-bound peripheral membrane proteins with lipid membranes.

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Section: Resultsmentioning

confidence: 89%

“…Recently, a free energy decrease of 15 kcal/mol was calculated for insertion of an sE trimer into a membrane containing 30% POPG 70% POPC (61). That study used a combined continuum and molecular dynamics approach.…”

Section: Resultsmentioning

confidence: 99%

Method for measuring the unbinding energy of strongly-bound membrane-associated proteins

Bauve

Vernon

et al. 2016

Biochimica et Biophysica Acta (BBA) - Biomembranes

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“…In a prior simulation study, the potential of mean force was determined for an E trimer as a function of distance with respect to a 70:30 PC:PG membrane [57]. In that work, the E trimer was fixed in a perpendicular orientation with respect to the membrane throughout the simulation.…”

Section: Discussionmentioning

confidence: 99%

Insertion of Dengue E into lipid bilayers studied by neutron reflectivity and molecular dynamics simulations

Vanegas

Heinrich

Rogers

et al. 2018

Biochimica et Biophysica Acta (BBA) - Biomembranes

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The envelope (E) protein of Dengue virus rearranges to a trimeric hairpin to mediate fusion of the viral and target membranes, which is essential for infectivity. Insertion of E into the target membrane serves to anchor E and possibly also to disrupt local order within the membrane. Both aspects are likely to be affected by the depth of insertion, orientation of the trimer with respect to the membrane normal, and the interactions that form between trimer and membrane. In the present work, we resolved the depth of insertion, the tilt angle, and the fundamental interactions for the soluble portion of Dengue E trimers (sE) associated with planar lipid bilayer membranes of various combinations of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC), 1-palmitoyl-2-oleoyl-sn-glycero-3-phospho-rac-glycerol (POPG), 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoethanolamine (POPE), and cholesterol (CHOL) by neutron reflectivity (NR) and by molecular dynamics (MD) simulations. The results show that the tip of E containing the fusion loop (FL) is located at the interface of the headgroups and acyl chains of the outer leaflet of the lipid bilayers, in good agreement with prior predictions. The results also indicate that E tilts with respect to the membrane normal upon insertion, promoted by either the anionic lipid POPG or CHOL. The simulations show that tilting of the protein correlates with hydrogen bond formation between lysines and arginines located on the sides of the trimer close to the tip (K246, K247, and R73) and nearby lipid headgroups. These hydrogen bonds provide a major contribution to the membrane anchoring and may help to destabilize the target membrane.

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“…Virtually all biological functions are pH-dependent (Casey et al, 2010); for viruses, pH changes are known to induce structural modifications in virion capsids required for specific steps in the infection process. Examples include the low pH-activated uncoating of human rhinoviruses (Suomalainen & Greber, 2013) and the low pH-triggered, viral membrane-host endosomal membrane fusion that occurs during the endocytosis of influenza and dengue viruses (Harrison, 2008;Fontana et al, 2012;Rogers et al, 2015). In the case of Cowpea chlorotic mottle virus, a beetle-transmitted plant virus in the genus Bromovirus (Mello et al, 2010), raising the pH from 5 to 7 induces capsid swelling, and this has been postulated to play a role in the release of virion RNA following virus entry into the cell (Tama & Brooks, 2002;Wilts et al, 2015).…”

Section: Introductionmentioning

confidence: 99%

Whitefly feeding behavior and retention of a foregut‐borne crinivirus exposed to artificial diets with different pH values

et al. 2017

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Transmission of plant viruses by phytophagous hemipteran insects encompasses complex interactions underlying a continuum of processes involved in virus acquisition, retention and inoculation combined with vector feeding behavior. Here, we investigated the effects of dietary pH on whitefly (Bemisia tabaci) feeding behavior and release of Lettuce infectious yellows virus (LIYV) virions retained in the vector's foregut. Electrical penetration graph analysis revealed that variables associated with whitefly probing and ingestion did not differ significantly in pH (4, 7.4, and 9) adjusted artificial diets. To investigate virus retention and release, whiteflies allowed to acquire LIYV virions in a pH 7.4 artificial diet were fed pH 4, 7.4, or 9 virion-free artificial (clearing) diets. Immunofluorescent localization analyses indicated that virions remained bound to the foreguts of approximately 20%-24% of vectors after they fed on each of the 3 pHadjusted clearing diets. When RNA preparations from the clearing diets were analyzed by reverse transcription (RT) nested-PCR and, in some cases, real-time qPCR, successful amplification of LIYV-specific sequence was infrequent but consistently repeatable for the pH 7.4 diet but never observed for the pH 4 and 9 diets, suggesting a weak pH-dependent effect for virion release. Viruliferous vectors that fed on each of the 3 pH-adjusted clearing diets transmitted LIYV to virus-free plants. These results suggest that changes in pH values alone in artificial diet do not result in observable changes in whitefly feeding behaviors, an observation that marks a first in the feeding of artificial diet by whitefly vectors; and that there is a potential causal and contingent relationship between the pH in artificial diet and the release/inoculation of foregut bound virions.

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Molecular basis of endosomal-membrane association for the dengue virus envelope protein

Cited by 19 publications

References 102 publications

Method for measuring the unbinding energy of strongly-bound membrane-associated proteins

Method for measuring the unbinding energy of strongly-bound membrane-associated proteins

Insertion of Dengue E into lipid bilayers studied by neutron reflectivity and molecular dynamics simulations

Whitefly feeding behavior and retention of a foregut‐borne crinivirus exposed to artificial diets with different pH values

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