Exploration of Conformational Spaces of High‐Mannose‐Type Oligosaccharides by an NMR‐Validated Simulation

Yamaguchi, Takumi; Sakae, Yoshitake; Zhang, Ying; Yamamoto, Sayoko; Okamoto, Yuko; Kato, Koichi

doi:10.1002/ange.201406145

Cited by 17 publications

(9 citation statements)

References 39 publications

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“…Canonical MD was selected in place of replica exchange MD, a very accurate but computer power-demanding approach (17). Replica exchange MD succeeds in determining the types and proportions of the different conformers, avoiding their trapping in local minima, but the two approaches converge when simulations are performed at high temperatures, with 300 K considered the lower limit (17,18). Hence, a NMR T-ROESY (transverse rotating-frame Overhauser enhancement spectroscopy) spectrum was recorded at 310 K, so that each MD simulation (310 K, 20 ns) reasonably sampled the space accessible to each oligosaccharide.…”

Section: Resultsmentioning

confidence: 99%

Structure of the chlorovirus PBCV-1 major capsid glycoprotein determined by combining crystallographic and carbohydrate molecular modeling approaches

Castro¹,

Klose

Speciale³

et al. 2017

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

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The glycans of the major capsid protein (Vp54) of chlorella virus (PBCV-1) were recently described and found to be unusual. This prompted a reexamination of the previously reported Vp54 X-ray structure. A detailed description of the complete glycoprotein was achieved by combining crystallographic data with molecular modeling. The crystallographic data identified most of the monosaccharides located close to the protein backbone, but failed to detect those further from the glycosylation sites. Molecular modeling complemented this model by adding the missing monosaccharides and examined the conformational preference of the whole molecule, alone or within the crystallographic environment. Thus, combining X-ray crystallography with carbohydrate molecular modeling resulted in determining the complete glycosylated structure of a glycoprotein. In this case, it is the chlorovirus PBCV-1 major capsid protein.

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Section: Resultsmentioning

confidence: 99%

Structure of the chlorovirus PBCV-1 major capsid glycoprotein determined by combining crystallographic and carbohydrate molecular modeling approaches

Castro¹,

Klose

Speciale³

et al. 2017

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

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“…A fold-back conformer of high-mannose-type oligosaccharides explored by combination of NMR and REMD is one of the examples. 15 Use of LEUS enables us to capture such conformers as well (see Figure S4 ). The difference between plain MD simulation and the LEUS simulation can be seen from Figure 9 B and C where 50 frames of the trajectories from plain MD and LEUS were randomly selected and aligned on the Asn residue.…”

Section: Resultsmentioning

confidence: 99%

“…The same technique was used to extensively sample complex glycans 14 and high mannose oligosaccharides. 15 Even though these studies provide understanding about conformational preferences of several disaccharides, either the studied systems and techniques are different or the sampling of all relevant conformations is insufficient. To the best of our knowledge, the current work represents a first description of a consistent conformational library for the vast majority of relevant linkages in mammalian glycans.…”

Section: Introductionmentioning

confidence: 99%

Modeling of Oligosaccharides within Glycoproteins from Free-Energy Landscapes

Turupcu

Oostenbrink

2017

J. Chem. Inf. Model.

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In spite of the abundance of glycoproteins in biological processes, relatively little three-dimensional structural data is available for glycan structures. Here, we study the structure and flexibility of the vast majority of mammalian oligosaccharides appearing in N- and O-glycosylated proteins using a bottom up approach. We report the conformational free-energy landscapes of all relevant glycosidic linkages as obtained from local elevation simulations and subsequent umbrella sampling. To the best of our knowledge, this represents the first complete conformational library for the construction of N- and O-glycan structures. Next, we systematically study the effect of neighboring residues, by extensively simulating all relevant trisaccharides and one tetrasaccharide. This allows for an unprecedented comparison of disaccharide linkages in large oligosaccharides. With a small number of exceptions, the conformational preferences in the larger structures are very similar as in the disaccharides. This, finally, allows us to suggest several efficient approaches to construct complete N- and O-glycans on glycoproteins, as exemplified on two relevant examples.

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“…Generally, oligosaccharides continuously change their conformation with a higher degree of motional freedom. The longer the sugar chain, the higher the motional freedom and the greater the fluctuation of the chain ( 49 ).…”

Section: Discussionmentioning

confidence: 99%

Alteration of Membrane Physicochemical Properties by Two Factors for Membrane Protein Integration

Nomura

Yamaguchi

Mori

et al. 2019

Biophysical Journal

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After a nascent chain of a membrane protein emerges from the ribosomal tunnel, the protein is integrated into the cell membrane. This process is controlled by a series of proteinaceous molecular devices, such as signal recognition particles and Sec translocons. In addition to these proteins, we discovered two endogenous components regulating membrane protein integration in the inner membrane of Escherichia coli . The integration is blocked by diacylglycerol (DAG), whereas the blocking is relieved by a glycolipid named membrane protein integrase (MPIase). Here, we investigated the influence of these integration-blocking and integration-promoting factors on the physicochemical properties of membrane lipids via solid-state NMR and fluorescence measurements. These factors did not have destructive effects on membrane morphology because the membrane maintained its lamellar structure and did not fuse in the presence of DAG and/or MPIase at their effective concentrations. We next focused on membrane flexibility. DAG did not affect the mobility of the membrane surface, whereas the sugar chain in MPIase was highly mobile and enhanced the flexibility of membrane lipid headgroups. Comparison with a synthetic MPIase analog revealed the effects of the long sugar chain on membrane properties. The acyl chain order inside the membrane was increased by DAG, whereas the increase was cancelled by the addition of MPIase. MPIase also loosened the membrane lipid packing. Focusing on the transbilayer movement, MPIase reduced the rapid flip-flop motion of DAG. On the other hand, MPIase could not compensate for the diminished lateral diffusion by DAG. These results suggest that by manipulating the membrane lipids dynamics, DAG inhibits the protein from contacting the inner membrane, whereas the flexible long sugar chain of MPIase increases the opportunity for interaction between the membrane and the protein, leading to membrane integration of the newly formed protein.

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Exploration of Conformational Spaces of High‐Mannose‐Type Oligosaccharides by an NMR‐Validated Simulation

Cited by 17 publications

References 39 publications

Structure of the chlorovirus PBCV-1 major capsid glycoprotein determined by combining crystallographic and carbohydrate molecular modeling approaches

Structure of the chlorovirus PBCV-1 major capsid glycoprotein determined by combining crystallographic and carbohydrate molecular modeling approaches

Modeling of Oligosaccharides within Glycoproteins from Free-Energy Landscapes

Alteration of Membrane Physicochemical Properties by Two Factors for Membrane Protein Integration

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