Mechanical Compressibility of the Glycosylphosphatidylinositol (GPI) Anchor Backbone Governed by Independent Glycosidic Linkages

Wehle, Marko; Vilotijević, Ivan; Lipowsky, Reinhard; Seeberger, Peter H.; Silva, Daniel Varón; Santer, Mark

doi:10.1021/ja302803r

Cited by 41 publications

(42 citation statements)

References 48 publications

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“…Structure optimization of the molecule was performed with Gaussian at the HF/6‐31G* level of theory, and the final set of charges was obtained from an ensemble average of 50 structures generated from a 20 ns MD trajectory. The topologies for F‐azo and DOPC were converted using the glycam2gmx.pl script 40. The system was solvated with TIP3P water 41.…”

Section: Methodsmentioning

confidence: 99%

Area Increase and Budding in Giant Vesicles Triggered by Light: Behind the Scene

et al. 2018

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Biomembranes are constantly remodeled and in cells, these processes are controlled and modulated by an assortment of membrane proteins. Here, it is shown that such remodeling can also be induced by photoresponsive molecules. The morphological control of giant vesicles in the presence of a water‐soluble ortho‐tetrafluoroazobenzene photoswitch (F‐azo) is demonstrated and it is shown that the shape transformations are based on an increase in membrane area and generation of spontaneous curvature. The vesicles exhibit budding and the buds can be retracted by using light of a different wavelength. In the presence of F‐azo, the membrane area can increase by more than 5% as assessed from vesicle electrodeformation. To elucidate the underlying molecular mechanism and the partitioning of F‐azo in the membrane, molecular dynamics simulations are employed. Comparison with theoretically calculated shapes reveals that the budded shapes are governed by curvature elasticity, that the spontaneous curvature can be decomposed into a local and a nonlocal contribution, and that the local spontaneous curvature is about 1/(2.5 µm). The results show that exo‐ and endocytotic events can be controlled by light and that these photoinduced processes provide an attractive method to change membrane area and morphology.

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Section: Methodsmentioning

confidence: 99%

Area Increase and Budding in Giant Vesicles Triggered by Light: Behind the Scene

et al. 2018

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“…The topology files were converted for use with the glycam2gmxRB.pl Perl script, kindly provided by Dr. Marko Wehle, which enabled a mixed 1-4 non-bonded scaling scheme to be used for the protein and carbohydrate force fields, as recommended. [72]–[74]. GROMACS v4.07 [75], [76] was used for setting up the system, as well as for all simulations.…”

Section: Methodsmentioning

confidence: 99%

The Influence of N-Linked Glycans on the Molecular Dynamics of the HIV-1 gp120 V3 Loop

et al. 2013

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N-linked glycans attached to specific amino acids of the gp120 envelope trimer of a HIV virion can modulate the binding affinity of gp120 to CD4, influence coreceptor tropism, and play an important role in neutralising antibody responses. Because of the challenges associated with crystallising fully glycosylated proteins, most structural investigations have focused on describing the features of a non-glycosylated HIV-1 gp120 protein. Here, we use a computational approach to determine the influence of N-linked glycans on the dynamics of the HIV-1 gp120 protein and, in particular, the V3 loop. We compare the conformational dynamics of a non-glycosylated gp120 structure to that of two glycosylated gp120 structures, one with a single, and a second with five, covalently linked high-mannose glycans. Our findings provide a clear illustration of the significant effect that N-linked glycosylation has on the temporal and spatial properties of the underlying protein structure. We find that glycans surrounding the V3 loop modulate its dynamics, conferring to the loop a marked propensity towards a more narrow conformation relative to its non-glycosylated counterpart. The conformational effect on the V3 loop provides further support for the suggestion that N-linked glycosylation plays a role in determining HIV-1 coreceptor tropism.

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“…Simulation files were generated using the tleap module of AmberTools12 (Case et al 2012), and subsequently converted to GROMACS format with the glycam2gmx.pl script from Wehle et al (2012). The double precision parallel implementation of the mdrun module from GROMACS 4.5.5 (Berendsen et al 1995; Hess et al 2008; van der Spoel et al 2011) was employed for all simulation work.…”

Section: Methodsmentioning

confidence: 99%

Effect of microfibril twisting on theoretical powder diffraction patterns of cellulose Iβ

2013

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Previous studies of calculated diffraction patterns for cellulose crystallites suggest that distortions that arise once models have been subjected to MD simulation are the result of both microfibril twisting and changes in unit cell dimensions induced by the empirical force field; to date, it has not been possible to separate the individual contributions of these effects. To provide a better understanding of how twisting manifests in diffraction data, the present study demonstrates a method for generating twisted and linear cellulose structures that can be compared without the bias of dimensional changes, allowing assessment of the impact of twisting alone. Analysis of unit cell dimensions, microfibril volume, hydrogen bond patterns, glycosidic torsion angles, and hydroxymethyl group orientations confirmed that the twisted and linear structures collected with this method were internally consistent, and theoretical powder diffraction patterns for the two were shown to be effectively indistinguishable. These results indicate that differences between calculated patterns for the crystal coordinates and twisted structures from MD simulation can result entirely from changes in unit cell dimensions, and not from microfibril twisting alone. Although powder diffraction patterns for models in the 81-chain size regime were shown to be unaffected by twisting, suggesting that a modest degree of twist is not inconsistent with experimental data, it may be that other diffraction techniques are capable of detecting this structural difference. Until such time as definitive experimental evidence comes to light, the results of this study suggest that both twisted and linear microfibrils may represent an appropriate model for cellulose Iβ.

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Mechanical Compressibility of the Glycosylphosphatidylinositol (GPI) Anchor Backbone Governed by Independent Glycosidic Linkages

Cited by 41 publications

References 48 publications

Area Increase and Budding in Giant Vesicles Triggered by Light: Behind the Scene

Area Increase and Budding in Giant Vesicles Triggered by Light: Behind the Scene

The Influence of N-Linked Glycans on the Molecular Dynamics of the HIV-1 gp120 V3 Loop

Effect of microfibril twisting on theoretical powder diffraction patterns of cellulose Iβ

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