Papers by Saskia van der Vies
Alzheimers & Dementia, Jul 1, 2014
the timing of symptom onset in ADAD. Methods: We have collected data on ages of symptom onset fro... more the timing of symptom onset in ADAD. Methods: We have collected data on ages of symptom onset from 390 ADAD pedigrees, compiled from 138 peer-reviewed publications, the Dominantly Inherited Alzheimer Network (DIAN) database, and two large kindreds of Colombian (PSEN1 E280A) and Volga German (PSEN2 N141I) ancestry. Our combined dataset includes 3282 individuals, of whom 1314 were affected by ADAD with known age of symptom onset. We assessed the relative contributions of several factors in influencing age of onset, including the affected gene and amino acid location of the ADAD mutation, parental age of onset, age of onset by mutation type and family, and APOE genotype and gender. We additionally performed a confirmatory survival analysis using data from 183 ADAD mutation carriers followed longitudinally in the DIAN study. Results: We report summary statistics on age of onset and disease course for 176 ADAD mutations, and discover strong and highly significant (p 0.38) correlations between individual age of symptom onset and predicted values based on parental age of onset and mean ages of onset by mutation type and family, which persist after controlling for APOE genotype and gender. Conclusions: Significant proportions of the observed variance in age of symptom onset in ADAD can be explained by the gene and amino acid location of ADAD mutations, providing empirical support for use of these data to estimate onset in clinical research.
Journal of Biological Chemistry, Mar 1, 1993
The native phytochrome photoreceptor was purified to homogeneity from etiolated seedlings of oat ... more The native phytochrome photoreceptor was purified to homogeneity from etiolated seedlings of oat (Avena sativa L.) and used for renaturation experiments. Light scattering measurements showed that the GroEL molecular chaperone interacts with non-native phytochrome to suppress aggregation of the refolding polypeptide, following its dilution from a chaotrope. The binary complex formed between non-native phytochrome and GroEL was stable and could be isolated by size exclusion chromatography. Discharge of the photoreceptor from GroEL was obtained with 2 m M MgATP, although 6 mM adenosine 6'-0-(3-thiotriphosphate) was also effective. Phytochrome released from GroEL with MgATP was found primarily in the form of 124-kDa monomers, as judged by size exclusion chromatography and nondenaturing gel electrophoresis, although dimers and other oligomeric forms were also observed. The reconstituted dimers, and other oligomeric forms, preferentially cross-reacted with a monoclonal antibody that recognizes native-like epitopes. In vitro folding reactions, using chemically denatured phytochrome, revealed that successful reconstitution of the photoreceptor required the presence of the GroEL chaperonin and MgATP under the conditions tested. Reconstitution in the presence of GroEL yielded phytochrome that could exhibit photoreversibility between the red-light absorbing and far-red absorbing forms. Phytochrome is a cytosolic photoreceptor that has a pivotal role in the regulation of numerous developmental responses in plants to light, including seed germination, stem elongation, and flowering (1,2). The involvement of the photoreceptor in the control of expression of a number of genes in these morphogenic responses has been characterized (3-5). The ability of phytochrome to function as a phototransducer resides in its characteristic property of existing in two possible forms that are reversibly interconvertible by light (6). The
Cell, Jul 1, 1997
M. van der Vies, † major capsid protein from bacteriophage T4, represents a singular exception to... more M. van der Vies, † major capsid protein from bacteriophage T4, represents a singular exception to this paradigm of promiscuity in Lisa Henry,* and Johann Deisenhofer* that it requires the replacement of GroES by Gp31, a *Howard Hughes Medical Institute and specialized co-chaperonin encoded by the bacterio-Department of Biochemistry phage (Laemmli et al., 1970; Doermann and Simon, 1984; The University of Texas Southwestern van der Vies et al., 1994). Medical Center The mechanism of GroEL/GroES-assisted protein Dallas, Texas 75235-9050 folding has been the subject of extensive investigation † Dé partement de Biochimie Mé dicale (Ellis, 1996; Hartl, 1996; Lorimer, 1996). It has been sug-Université de Genè ve gested that the GroEL/GroES complex may assist pro-1211 Genè ve 4 tein folding using more than one mechanism in parallel Switzerland (Schmidt et al., 1994; Todd et al., 1994; Corrales and Fersht, 1996). However, so far only one mechanism has substantial support from in vitro biochemical studies Summary (Mayhew et al., 1996; Weissman et al., 1996; Hayer-Hartl et al., 1996). This mechanism involves the encapsulation The Gp31 protein from bacteriophage T4 functionally of the non-native polypeptide substrate in the so-called substitutes for the bacterial co-chaperonin GroES in ''Anfinsen cage'' (Saibil et al., 1993; Ellis, 1994), i.e., the assisted protein folding reactions both in vitro and cavity formed within the hollow core of one heptameric in vivo. But Gp31 is required for the folding and/or GroEL cylinder when capped by the GroES dome (Saibil assembly of the T4 major capsid protein Gp23, and et al., 1991; Langer et al., 1992; Roseman et al., 1996). this requirement cannot be satisfied by GroES. The Kinetic analyses have shown that protein folding can 2.3 Å crystal structure of Gp31 shows that its tertiary proceed passively within this cavity for at least some and quaternary structures are similar to those of substrates (Weissman et al., 1995; Walter et al., 1996), GroES despite the existence of only 14% sequence suggesting that the major purpose of the chaperonin identity between the two proteins. However, Gp31 complex may be to provide a chemically sequestered shows a series of structural adaptations which will environment where folding to the native state can proincrease the size and the hydrophilicity of the ''Anfinceed without interference from the reservoir of aggregasen cage,'' the enclosed cavity within the GroEL/ tion-prone species in the crowded molecular environ-GroES complex that is the location of the chaperoninment of the cell (Ellis, 1994). Such a passive reaction assisted protein folding reaction. mechanism is consistent with the established molecular promiscuity of the chaperonins.
American Chemical Society eBooks, Apr 22, 1993
... Molecular Chaperones and Their Role in Protein Assembly Saskia M. van der Vies1, Anthony A. G... more ... Molecular Chaperones and Their Role in Protein Assembly Saskia M. van der Vies1, Anthony A. Gatenby2, Paul V. Viitanen2, and George H. Lorimer2 ... 68. Buchner, J.; Schmidt, M.; Fuchs, M.; Jaenicke, R.; Rudolph, R.; Schmid, FX; Kiefhaber, T. Biochemistry 1991, 30, 1586. 69. ...
European journal of biochemistry, Oct 1, 1987
A cDNA clone for the precursor form of the small subunit of wheat ribulose-bisphosphate carboxyla... more A cDNA clone for the precursor form of the small subunit of wheat ribulose-bisphosphate carboxylase has been modified to allow the expression in Escherichia coli of a mature form of small subunit that lacks the transit peptide. Synthesis of the protein is controlled by a lac promoter, and translation is initiated from a lacZ ribosome binding site, giving rise to a small subunit with several beta-galactosidase amino acids fused to its N-terminus. A plasmid has been constructed that enables both wheat small subunits and maize large subunits to be synthesized in the bacterial cell, but using different promoters to allow independent expression of the rbcS and rbcL genes. When the small subunit is synthesized in the absence of the large subunit, it is found in the soluble fraction but the polypeptide is unstable and has a half-life of less than 15 min. Its size on sucrose gradients indicates a monomeric or dimeric form. When large subunit synthesis is induced in cells containing the small subunit, both subunits are found predominantly in the insoluble fraction and are fully stable for more than 120 min, suggesting that aggregation of the subunits may occur. The two subunits do not assemble together to form an active holoenzyme in vivo, even when nascent large subunits ware synthesized in a pool of mature small subunits. This indicates that other factors may be required to mediate the assembly of the higher plant enzyme.
Humana Press eBooks, Nov 14, 2003
Nature, Apr 1, 1994
Several bacteriophages use the Escherichia coli GroES and GroEL chaperonins for folding and assem... more Several bacteriophages use the Escherichia coli GroES and GroEL chaperonins for folding and assembly of their morphogenetic structures. Bacteriophage T4 is unusual in that it encodes a specialized protein (Gp31) that is thought to interact with the host GroEL and to be absolutely required for the correct assembly of the major capsid protein (Gp23) in vivo. Here we show that despite the absence of amino-acid sequence similarity between Gp31 and GroES, Gp31 can functionally substitute for the GroES co-chaperonin in the morphogenesis of bacteriophages lambda and T5, the in vivo and in vitro chaperonin-dependent assembly of ribulose bisphosphate carboxylase (Rubisco), as well as overall bacterial growth at the non-permissive temperature. Like GroES, the bacteriophage Gp31 protein forms a stable complex with the E. coli GroEL protein in the presence of Mg-ATP and inhibits the ATPase activity of GroEL in vitro.
Acs Symposium Series, Jul 23, 1993
... Anthony A. Gatenby, Gail K. Donaldson, François Baneyx, George H. Lorimer, Paul V. Viitanen, ... more ... Anthony A. Gatenby, Gail K. Donaldson, François Baneyx, George H. Lorimer, Paul V. Viitanen, and Saskia M. van der Vies ... 51. Buchner, J.; Schmidt, M.; Fuchs, M.; Jaenicke, R.; Rudolph, R.; Schmid, F. X.; Kiefhaber, T. Biochemistry 1991, 30, 1586. 52. ...
Alzheimer's & Dementia, 2014
tissue. Methods: Frozen brain tissue from healthy controls (HCs) and neuropathologically confirme... more tissue. Methods: Frozen brain tissue from healthy controls (HCs) and neuropathologically confirmed cases of AD (CERAD criteria) were obtained from the Douglas-Bell Canada Brain Bank (Douglas Mental Health University Institute, Montreal, Canada). In total, 26 samples from the hippocampus (HIPP) (HC1⁄419, AD1⁄47), 18 from the prefrontal cortex (PFC) (HC1⁄414, AD1⁄44), 20 from the posterior cingulate cortex (PCC) (HC 1⁄4 11, AD 1⁄4 9) and 22 from the inferior parietal cortex (IPC) (HC1⁄415, A1⁄47)were included.[18 F]T807 autoradiography (specific activity, > 71,000 mCi/micromol) was carried out following 2.5-hour incubation of frozen tissue slices (20 mm thick). Imaging plates were scanned using BAS5000 Phosphoimager (Fuji-Film), with total binding obtained for all regions of interest. Results: No significant differences between control and AD groups were noted in terms of sex distribution, age and postmortem delay (P < 0.05). Binding of [18 F]T807 was significantly higher in AD tissue, as compared to CN [HIPP (P < 0.01), PFC (P < 0.01), IPC (P < 0.05), PCC (P < 0.05], with the magnitude of difference highest in the IPC. Conclusions: [18 F]T807 successfully differentiated CN and AD post-mortem tissue, with binding substantially higher in AD, particularly in the IPC. Our findings support the current perspective on [18 F]T807 as a promising tau molecular imaging agent.
Chaperonin Protocols
Page 1. Chaperonin Activity In Vivo 75 9 Determination of Chaperonin Activity In Vivo Saskia M. v... more Page 1. Chaperonin Activity In Vivo 75 9 Determination of Chaperonin Activity In Vivo Saskia M. van der Vies and Pete A. Lund 1. Introduction During the last 10 years, much effort has been made to unravel the molecu-lar mechanism ...
International Journal of Mass Spectrometry, Sep 1, 2007
... Thumbnails - selected | Full-Size images. Article. Article - selected. Figures/Tables. Figure... more ... Thumbnails - selected | Full-Size images. Article. Article - selected. Figures/Tables. Figures/Tables - selected. References. References - selected. International Journal of Mass Spectrometry Volume 265, Issues 2-3, 1 September 2007, Pages 159-168 Jean H. Futrell Honour Issue ...
Rapid Communications in Mass Spectrometry, Oct 29, 2008
Many biological active proteins are assembled in protein complexes. Understanding the (dis)assemb... more Many biological active proteins are assembled in protein complexes. Understanding the (dis)assembly of such complexes is therefore of major interest. Here we use mass spectrometry to monitor the disassembly induced by thermal activation of the heptameric co-chaperonins GroES and gp31. We use native electrospray ionization mass spectrometry (ESI-MS) on a Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometer to monitor the stoichiometry of the chaperonins. A thermally controlled electrospray setup was employed to analyze conformational and stoichiometric changes of the chaperonins at varying temperature. The native ESI-MS data agreed well with data obtained from fluorescence spectroscopy as the measured thermal dissociation temperatures of the complexes were in good agreement. Furthermore, we observed that thermal denaturing of GroES and gp31 proceeds via intermediate steps of all oligomeric forms, with no evidence of a transiently stable unfolded heptamer. We also evaluated the thermal dissociation of the chaperonins in the gas phase using infrared multiphoton dissociation (IRMPD) for thermal activation. Using gas-phase activation the smaller (2-4) oligomers were not detected, only down to the pentamer, whereafter the complex seemed to dissociate completely. These results demonstrate clearly that conformational changes of GroES and gp31 due to heating in solution and in the gas phase are significantly different.
Annual Review of Biochemistry, Jun 1, 1991
Page 1. Annu. Rev. Biochem. 1991. 60:321-47 Copyright й 1991 by Annual Reviews Inc. All rights re... more Page 1. Annu. Rev. Biochem. 1991. 60:321-47 Copyright й 1991 by Annual Reviews Inc. All rights reserved MOLECULAR CHAPERONES R . John Ellis Department of Biological Sciences, University of Warwick, Coventry, United Kingdom Saskia M. van der Vies ...
Photosynthesis Research, Apr 1, 1988
Chloroplasts contain an abundant soluble protein that binds non-covalently newly synthesized larg... more Chloroplasts contain an abundant soluble protein that binds non-covalently newly synthesized large and small subunits of the enzyme ribulose bisphosphate carboxylase-oxygenase. This binding protein has been purified from Pisum sativum and Hordeum vulgare in the form of a dodecamer consisting of equal amounts of two types of subunit. These subunits are synthesized as higher molecular mass precursors by cytoplasmic ribosomes before import into the chloroplast. Antibodies raised against the purified binding protein from Pisum sativum detect polypeptides not only in extracts of plastids from several plant species but also in cell extracts of several bacterial species. The oligomeric binding protein dissociates reversibly into monomeric subunits in the presence of 1-5 mmol/liter MgATP. For one type of subunit the cDNA sequence has been isolated and determined and reveals homology with certain bacterial proteins.These observations are discussed in relation to the idea that the binding protein is an example of a general class of proteins termed &quot;molecular chaperones&quot; which are required for the correct assembly of certain oligomeric proteins such as the carboxylase from their subunits.
European journal of biochemistry, Mar 3, 2005
Analytical Chemistry, Sep 14, 2006
Electron capture dissociation (ECD) of proteins in Fourier transform ion cyclotron resonance mass... more Electron capture dissociation (ECD) of proteins in Fourier transform ion cyclotron resonance mass spectrometry usually leads to charge reduction and backbone-bond cleavage, thereby mostly retaining labile, intramolecular noncovalent interactions. In this report, we evaluate ECD of the 84-kDa noncovalent heptameric gp31 complex and compare this with sustained off-resonance irradiation collisionally activated dissociation (SORI-CAD) of the same protein. Unexpectedly, the 21+ charge state of the gp31 oligomer exhibits a main ECD pathway resulting in a hexamer and monomer, disrupting labile, intermolecular noncovalent bonds and leaving the backbone intact. Unexpectedly, the charge separation over the two products is highly proportional to molecular weight. This indicates that a major charge redistribution over the subunits of the complex does not take place during ECD, in contrast to the behavior observed when using SORI-CAD. We speculate that the ejected monomer retains more of its original structure in ECD, when compared to SORI-CAD. ECD of lower charge states of gp31 does not lead to dissociation of noncovalent bonds. We hypothesize that the initial gas-phase structure of the 21+ charge state is significantly different from the lower charge states. These structural differences result in the different reaction pathways when using ECD.
Biochemical Society Transactions, Oct 1, 1988
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Papers by Saskia van der Vies