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Results for “Protein Isoforms”

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PubMed2001

HMGN3a and HMGN3b, two protein isoforms with a tissue-specific expression pattern, expand the cellular repertoire of nucleosome-binding proteins.

HMGN1 (HMG-14) and HMGN2 (HMG-17) are nuclear proteins that bind specifically to nucleosomes, reduce the compactness of the chromatin fiber, and enhance transcription from chromatin templates. Here we report that many vertebrates contain an additional type of HMGN protein named HMGN3 (Trip 7). The human HMGN3 gene is located on chromosome 6 and spans 32 kilobase pairs, which is nearly 10-fold longer than the closely related HMGN2 gene. However, the intron/exon boundaries of the HMGN3 gene are identical to those of HMGN1 and HMGN2. Unique within the HMGN family, the HMGN3 transcript undergoes alternative splicing and generates two different variants, HMGN3a and HMGN3b. The shorter variant, HMGN3b, arises from an additional splice site that truncates exon V and causes a frameshift. The resulting HMGN3b protein lacks the majority of the C-terminal chromatin-unfolding domain. Both splice variants are found in many vertebrates from frogs to man and are expressed in many tissues. The pattern of tissue-specific expression differs considerably from those of HMGN1 and HMGN2 at both the mRNA and the protein level. Our results expand the multiplicity of the HMGN protein family and raise the possibility that these nucleosome-binding proteins function as co-activators in tissue-specific gene expression.

Amino Acid Sequence↗

PubMed1998

Structure of the Drosophila projectin protein: isoforms and implication for projectin filament assembly.

The protein composition of the various muscle types in Drosophila melanogaster has been studied quite thoroughly and the analysis has revealed many differences involving the usage of muscle specific isoforms of a given protein, as well as the presence of proteins restricted to one muscle type. Drosophila projectin, the giant protein component of the third filament is quite unusual as it not only shows specific isoforms in various muscle types, but these isoforms are located at different sarcomeric locations, I band in the IFM and A band in synchronous muscles. This may suggest distinct functions for the projectin protein in various muscles, as well as a different set of protein interactions for each projectin isoform. Projectin is encoded by a single gene and the isoforms were proposed to be the result of alternative splicing of a primary transcript. Here, we report the nearly complete sequence of Drosophila projectin, as well as the possible splicing patterns used to generate different isoforms. The overall domain organization in projectin is composed of repeated motifs I and II in a few specific patterns, similar to its Caenorhabditis homolog, twitchin. Sequence similarity between twitchin and projectin further suggests how some domains may possibly be important for protein interactions and/or functions. Alternative splicing operates at the COOH terminus, leading to a shorter projectin protein lacking some of the terminal motifs II and unique sequence. These isoforms are discussed in view of projectin differential size and localization.

Alternative Splicing↗

PubMed2006

Altered beta-amyloid precursor protein isoforms in Mexican Alzheimer's Disease patients.

OBJECTIVE: To determine the beta-amyloid precursor protein (betaAPP) isoforms ratio as a risk factor for Alzheimer's Disease and to assess its relationship with demographic and genetic variables of the disease. METHODS: Blood samples from 26 patients fulfilling NINCDS-ADRDA diagnostic criteria for AD and 46 healthy control subjects were collected for Western blotting for betaAPP. A ratio of betaAPP isoforms, in optical densities, between the upper band (130 Kd) and the lower bands (106-110 Kd) was obtained. Odds ratios were obtained to determine risk factor of this component. RESULTS: betaAPP ratio on AD subjects was lower than that of control subjects: 0.3662 +/- 0.1891 vs. 0.6769 +/- 0.1021 (mean +/- SD, p<0.05). A low betaAPP ratio (<0.6) showed an OR of 4.63 (95% CI 1.45-15.33). When onset of disease was taken into account, a betaAPP ratio on EOAD subjects of 0.3965 +/- 0.1916 was found vs. 0.3445 +/- 0.1965 on LOAD subjects (p>0.05). CONCLUSIONS: Altered betaAPP isoforms is a high risk factor for Alzheimer's disease, although it has no influence on the time of onset of the disease.

Aged↗

PubMed2000

Tau protein isoforms, phosphorylation and role in neurodegenerative disorders.

Tau proteins belong to the family of microtubule-associated proteins. They are mainly expressed in neurons where they play an important role in the assembly of tubulin monomers into microtubules to constitute the neuronal microtubules network. Microtubules are involved in maintaining the cell shape and serve as tracks for axonal transport. Tau proteins also establish some links between microtubules and other cytoskeletal elements or proteins. Tau proteins are translated from a single gene located on chromosome 17. Their expression is developmentally regulated by an alternative splicing mechanism and six different isoforms exist in the human adult brain. Tau proteins are the major constituents of intraneuronal and glial fibrillar lesions described in Alzheimer's disease and numerous neurodegenerative disorders referred to as 'tauopathies'. Molecular analysis has revealed that an abnormal phosphorylation might be one of the important events in the process leading to their aggregation. Moreover, a specific set of pathological tau proteins exhibiting a typical biochemical pattern, and a different regional and laminar distribution could characterize each of these disorders. Finally, a direct correlation has been established between the progressive involvement of the neocortical areas and the increasing severity of dementia, suggesting that pathological tau proteins are reliable marker of the neurodegenerative process. The recent discovery of tau gene mutations in frontotemporal dementia with parkinsonism linked to chromosome 17 has reinforced the predominant role attributed to tau proteins in the pathogenesis of neurodegenerative disorders, and underlined the fact that distinct sets of tau isoforms expressed in different neuronal populations could lead to different pathologies.

Animals↗

PubMed2006

Tip60 protein isoforms and altered function in skin and tumors that overexpress ornithine decarboxylase.

Elevated expression of ornithine decarboxylase (ODC) and increased synthesis of polyamines are hallmarks of epithelial tumorigenesis. The skin and tumors of K6/ODC and ODC/Ras transgenic mice, in which overexpression of ODC has been targeted to hair follicles, were found to exhibit intrinsically high histone acetyltransferase (HAT) activity. We identified Tip60 as a candidate enzyme for contributing significantly to this abnormally high HAT activity. Compared with normal littermate controls, the levels of Tip60 protein and an alternative splice variant Tip53 were found to be greater in K6/ODC mouse skin. Furthermore, skin tumors that spontaneously develop in ODC/Ras bigenic mice typically have substantially more Tip60 protein than adjacent non-tumor-bearing skin and exhibit a unique pattern of Tip60 size variants and chemically modified protein isoforms. Steady-state Tip60 and Tip53 mRNA levels were not affected in ODC-overexpressing skin and tumors, implying novel posttranscriptional regulation by polyamines. Given the diverse roles of Tip60, the overabundance of Tip60 protein is predicted to have biological consequences. Compared with normal littermate skin, we detected altered association of Tip60 with E2F1 and a subset of newly identified Tip60-interacting transcription factors in ODC transgenic mouse skin and tumors. E2F1 was shown to be bound in greater amounts to up-regulated target genes in ODC-overexpressing skin. Thus, up-regulation of Tip60 protein, influencing the expression of Tip60-regulated genes, could play a contributing role in polyamine-mediated tumor promotion. (

Animals↗

PubMed1997

Alternative splicing of a novel glycophorin allele GPHe(GL) generates two protein isoforms in the human erythrocyte membrane.

The Henshaw antigen (synonym: He or MNS6) is carried by an altered form of glycophorin B (GPB), but the molecular basis for its variable expression or quantitative polymorphism remains largely undefined. We report here the identification and analysis of a novel glycophorin He allele, GPHe(GL), which gives rise to the expression of two protein isoforms in the erythrocyte membrane. In addition to the nucleotide changes defining the epitopic sequence of He, a single C-to-G nucleotide transversion in exon V coding for the membrane domain was found to cause aberrant RNA splicings by creating a new acceptor splice site. In addition, a T-to-G transversion at -6 position of the acceptor splice site for exon IV was identified. Both full-length and truncated transcripts of GPHe(GL) were detected as the result of partial activation of the new acceptor splice site and partial inactivation of the normal splice sites. The full-length cDNA encoded He, S, and U antigens, whereas the three truncated ones lacked either the sequence for S and U antigens or a large portion of the membrane domain or both. The GPB gene on the other chromosome was apparently normal and its transcript encoded N, s, and U antigens. These results correlate alternative RNA splicing with the expression of two GPHe isoforms and thus delineate a new mechanism for the phenotypic diversity of membrane glycophorins.

Alleles↗

PubMed1994

Expression of Na-K-ATPase alpha- and beta-subunit mRNA and protein isoforms in the rat nephron.

Na-K-ATPase is a heterodimeric complex composed of an alpha-catalytic and a glycosylated beta-subunit. Previous studies using in situ hybridization and Northern blot analysis to determine alpha- and beta-subunit mRNA isoform expression in the rat kidney have given conflicting results. This heterogeneity may be due to detection of alpha 2- or alpha 3-isoforms arising from nonrenal epithelial sources such as peripheral nerves or vascular smooth muscle. To address this possibility, we investigated alpha-subunit mRNA isoform expression in different nephron segments using tubule microdissection and reverse transcription-polymerase chain reaction amplification. Southern blot analysis of polymerase chain reaction products using isoform-specific primers and probes detected the expression of alpha 1- and alpha 3-mRNA isoforms in whole kidney, cortical collecting ducts (CCD), and proximal tubule S2 subsegments (S2). No evidence for alpha 2 was found in kidney or microdissected CCD or S2. To determine whether alpha 1- or alpha 3-mRNA in the CCD or S2 is translated into protein, Western blot analysis of total protein from microdissected S2, CCD, medullary thick ascending limb (MTAL), or outer medullary collecting duct outer stripe (OMCDos) was performed. Total protein was separated according to size by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, then probed using polyclonal antibodies specific for the alpha 1-, alpha 2-, alpha 3-, beta 1-, and beta 2-protein isoforms. Rat brain was used as a positive control and demonstrated that the antibodies could detect a single 97- and 35-kDa band for the alpha- and beta-isoforms, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1996

Contractile properties and protein isoforms of single fibres from the chicken pectoralis red strip muscle.

1. The contractile properties of single muscle fibres of the red strip region of adult chicken pectoralis major (PM) muscle, some of which are known to express an embryonic isoform of myosin heavy chain (MHC), were determined and compared with the properties of the fast white fibres of the PM and the slow tonic fibres of the anterior latissimus dorsi (ALD) muscle. 2. The red strip fibres could be classified into two groups, fast and slow. The mean velocity of unloaded shortening (Vmax) in fast red strip fibres was approximately half the Vmax of fast white fibres. Vmax of slow red strip fibres was less than 20% of the value for fast red strip fibres and was not different from Vmax of ALD fibres. 3. The tension-generating ability, i.e. the maximal isometric tension/fibre cross-sectional area (P0/CSA), was the same in fast red strip fibres and fast white fibres. P0/CSA was approximately 30% lower in slow red strip fibres compared with fast red strip fibres but was 70% greater in slow red strip fibres compared with ALD fibres. 4. The tension-pCa relation of fast red strip fibres was shifted to lower pCa values, indicating a lower calcium sensitivity compared with fast white fibres, and this difference was associated with a difference in troponin T isoform composition. The tension-pCa relation of slow red strip fibres was not different from that in ALD fibres. 5. The difference in Vmax between fast red strip fibres and fast white fibres was associated with different MHC compositions of these fibres. 6. The myofibrillar protein isoform composition of slow red strip fibres was identical to that of the slow tonic fibres of ALD muscle and these two groups of fibres had very similar contractile properties.

Animals↗

PubMed2005

Assembly of tubulin by classic myelin basic protein isoforms and regulation by post-translational modification.

Myelin basic protein (MBP), a highly cationic protein that maintains the structure of the myelin sheath, associates with tubulin in vivo. The in vitro assembly of tubulin by MBP was examined here using several assays. The unmodified C1 component of 18.5 kDa bovine MBP (bC1) assembled tubulin into microtubules in a dose-dependent manner via filamentous intermediates, and was able simultaneously to promote the formation of microtubule bundles. The critical tubulin concentration in the presence of bC1 was 0.69 +/- 0.05 microM. The effects of post-translational modifications (such as deamidation and phosphorylation) were assayed by comparing the bC1-bC6 components of 18.5 kDa bovine MBP; an increasing level of modification enhanced the ability of MBP to assemble tubulin. The effects of charge reduction via deimination were examined using recombinant murine isoforms emulating the unmodified C1 and deiminated C8 isoforms of 18.5 kDa MBP; both rmC1 and rmC8 exhibited a comparable ability to assemble tubulin. The effects of alternate exon recombination of the classic MBP variants were tested using the recombinant murine 21.5, 17.22, and 14 kDa isoforms. The isoforms containing regions derived from exon II of the classic MBP gene, 21.5 and 17.22 kDa MBP, showed no substantial difference in the extent of tubulin polymerization and bundling when compared to those of 18.5 kDa MBP. The 14 kDa isoform and two terminal deletion mutants of rmC1 were able to induce microtubule polymerization, but not bundling, to the same degree as the longer proteins. Finally, bC1 was shown to disrupt and aggregate planar sheets of crystalline tubulin stabilized by paclitaxel, establishing that these structures are not suitable substrates for the formation of MBP cocrystals.

Biopolymers↗

PubMed1998

Fatty acid binding protein isoforms: structure and function.

Although structural aspects of cytosolic fatty acid binding proteins (FABPs) in mammalian tissues are now well understood, significant advances regarding the physiological function(s) of these proteins have been slow in forthcoming. Part of the difficulty lies in the complexity of the multigene FABP family with nearly twenty identified members. Furthermore, isoelectric focusing and ion exchange chromatography operationally resolve many of the mammalian native FABPs into putative isoforms. However, a more classical biochemical definition of an isoform, i.e. proteins differing by a single amino acid, suggests that the operational definition is too broad. Because at least one putative heart H-FABP isoform, the mammary derived growth inhibitor, was an artifact (Specht et al. (1996) J. Biol. Chem. 271: 1943-49), the ensuing skepticism and confusion cast doubt on the existence of FABP isoforms in general. Yet, increasing data suggest that several FABPs, e.g. human intestinal I-FABP, bovine and mouse heart H-FABP, rabbit myelin P2 protein and bovine liver L-FABP may exist as true isoforms. In contrast, the rat liver L-FABP putative isoforms may actually be due either to bound ligand, post-translational S-thiolation and/or structural conformers. In any case, almost nothing is known regarding possible functions of either the true or putative isoforms in vitro or in vivo. The objective of this article is to critically evaluate which FABPs form biochemically defined or true isoforms versus FABPs that form additional forms, operationally defined as isoforms. In addition, recent developments in the molecular basis for FABP true isoform formation, the processes leading to additional operationally defined putative isoforms and insights into potential function(s) of this unusual aspect of FABP heterogeneity will be examined.

Animals↗

PubMed2001

Strategy for protein isoform identification from expressed sequence tags and its application to peptide mass fingerprinting.

Expressed Sequence Tags (ESTs) are an invaluable resource for protein identification and characterisation in proteomics. They allow proteins to be identified in the absence of genome sequence data. When EST sequences are used for protein identification, they are usually first processed into contigs to reduce redundancy and generate longer sequences from the overlapping ESTs. However, the process of generating contigs may accidentally group biologically meaningful isoforms together. Here we report means of discovering isoforms in EST sequences and how to use this information in the framework of protein identification and characterisation with peptide mass fingerprinting. We illustrate our strategies with examples from the dbEST database as well as protein isoforms from two-dimensional polyacrylamide gels.

Amino Acid Sequence↗

PubMed2003

The histone deacetylase 9 gene encodes multiple protein isoforms.

Histone deacetylases (HDACs) perform an important function in transcriptional regulation by modifying the core histones of the nucleosome. We have now fully characterized a new member of the Class II HDAC family, HDAC9. The enzyme contains a conserved deacetylase domain, represses reporter activity when recruited to a promoter, and utilizes histones H3 and H4 as substrates in vitro and in vivo. HDAC9 is expressed in a tissue-specific pattern that partially overlaps that of HDAC4. Within the human hematopoietic system, expression of HDAC9 is biased toward cells of monocytic and lymphoid lineages. The HDAC9 gene encodes multiple protein isoforms, some of which display distinct cellular localization patterns. For example, full-length HDAC9 is localized in the nucleus, but the isoform lacking the region encoded by exon 7 is in the cytoplasm. HDAC9 interacts and co-localizes in vivo with a number of transcriptional repressors and co-repressors, including TEL and N-CoR, whose functions have been implicated in the pathogenesis of hematological malignancies. These results suggest that HDAC9 plays a role in hematopoiesis; its deregulated expression may be associated with some human cancers.

Alternative Splicing↗

PubMed2001

Identification of a novel C-terminal domain involved in the negative function of the rainbow trout Ah receptor nuclear translocator protein isoform a (rtARNTa) in Ah receptor-mediated signaling.

Rainbow trout aryl hydrocarbon receptor (AHR) nuclear translocator isoform a (rtARNTa) has a negative function in AHR-mediated signal transduction. Previous analyses suggest that the negative function is at the level of DNA binding and may be due to the presence of 57 C-terminal amino acids that are strongly hydrophobic. To assess the negative activity of rtARNTa at the molecular level, hydrophobic-rich domains corresponding to amino acids 601-637, 601-631, and 616-631 were analyzed for the ability to affect the function of truncated rtARNT proteins in complementation and gel shift assays. Addition of the hydrophobic-rich domains to these proteins reduced their ability to complement AHR-mediated signal transduction in mouse hepatoma cells by 65-95%. The decrease in function was related to a reduced ability of the AHR. rtARNT complex to bind DNA and not due to a lack of dimerization with AHR. Expression of the hydrophobic-rich domains on Gal4 proteins showed that the C-terminal domain of rtARNTa was unlikely to contain transactivation function; however, the hydrophobic domains reduced the ability of the Gal4 proteins to bind DNA. Immunoprecipitation and mutational experiments indicate that the hydrophobic-rich domains do not interact with the bHLH motif of AHR. Interestingly, immunoprecipitation experiments also revealed that the C-terminal hydrophobic-rich region of rtARNTa could oligomerize in vitro in a chimera with the Gal4 DNA binding domain. These findings indicate that the C-terminal hydrophobic amino acids are critical for the negative function of rtARNTa in AHR-mediated signaling and suggest that multiple mechanisms may be involved in the repression of DNA binding.

Animals↗

PubMed2000

The tissue-specific, alternatively spliced single ATG exon of the type 3 voltage-dependent anion channel gene does not create a truncated protein isoform in vivo.

Voltage-dependent anion channels (VDACs) are small, integral membrane proteins that traverse the outer mitochondrial membrane and conduct ATP and other small metabolites. They are known to bind several kinases of intermediary metabolism in a tissue-specific fashion, have been found in close association with the adenine nucleotide translocator of the inner mitochondrial membrane, and are hypothesized to form part of the mitochondrial permeability transition pore, which results in the release of cytochrome c at the onset of apoptotic cell death. VDACs are found throughout all strata of eukaryotic evolution and exhibit biophysical characteristics that are well conserved from yeast to mammals. The mammalian VDAC gene family consists of three isoforms, each of which shares approximately 70% sequence identity with the other two family members. Recently, we reported that a single codon (ATG) exon is alternatively spliced into the transcript of the type 3 voltage-dependent anion channel (VDAC3) in a tissue-specific fashion. This unusual splicing event was shown to be conserved between mouse and human, and we theorized that the spliced exon could lead to the creation of an alternative translational initiation site. Here we report that a highly specific polyclonal VDAC3 antibody was unable to detect the truncated protein isoform indicative of this putative downstream start site. From these in vivo studies, we conclude that the alternatively spliced exon results in the insertion of a single methionine residue at amino acid position 39 of the mature VDAC3 protein. Additionally, we have used a cross-species genomic sequence comparison to identify conserved regions that may be involved in the regulation of small exon splicing.

Alternative Splicing↗

PubMed2004

A previously unidentified MECP2 open reading frame defines a new protein isoform relevant to Rett syndrome.

Rett syndrome is caused by mutations in the gene MECP2 in approximately 80% of affected individuals. We describe a previously unknown MeCP2 isoform. Mutations unique to this isoform and the absence, until now, of identified mutations specific to the previously recognized protein indicate an important role for the newly discovered molecule in the pathogenesis of Rett syndrome.

Base Sequence↗

PubMed2002

Effects of aging on human skeletal muscle myosin heavy-chain mRNA content and protein isoform expression.

The purpose of this investigation was to determine the role played by pretranslational events in the decreased rate of myosin heavy-chain (MyHC) protein synthesis in old age. It was hypothesized that the decreased rate of MyHC protein synthesis reported in the elderly population is, at least in part, related to lower MyHC messenger RNA (mRNA) in old age. MyHC protein expression and mRNA levels for the three MyHC isoforms expressed in human muscle, that is, types I, IIa, and IIx/d, were measured in percutaneous vastus lateralis muscle biopsies from 16 young and 16 old healthy men. The MyHC isoform mRNA content was determined by quantitative, real-time reverse transcriptase polymerase chain reaction, and it was normalized to 18S ribosomal RNA; the relative MyHC protein isoform content was measured on silver-stained 7% sodium dodecyl sulfate-polyacrylamide gel electrophoresis gels. The old men demonstrated signs of sarcopenia, such as loss of muscle force, a trend toward a loss in lean body mass, and an increased percentage of body fat. Statistically significant correlations were observed between the isoform expression of different MyHCs at the protein and mRNA levels. However, the expression of the different MyHC isoforms at the mRNA and protein levels did not differ between the young and old men. Thus, the present results do not support the hypothesis that pretranslational events in MyHC protein synthesis are playing a significant role in the development of sarcopenia.

Adult↗

PubMed1996

Fluorescently labeled phosphatidylinositol transfer protein isoforms (alpha and beta), microinjected into fetal bovine heart endothelial cells, are targeted to distinct intracellular sites.

Upon permeabilization of Swiss mouse 3T3 fibroblasts, an isoform of phosphatidylinositol transfer protein (PI-TP) was preferentially retained, a major part of which was associated with the perinuclear Golgi system (K. J. de Vries, A. Momchilova-Pankova, G. T. Snoek, and K. W. A. Wirtz, Exp. Cell Res. 215, 109-113, 1994). In the present study, the intracellular localization of this isoform (PI-TP beta) and the regular form (PI-TP alpha) was investigated in fetal bovine heart endothelial cells by microinjection of fluorescently labeled analogs followed by confocal laser scanning microscopy. The PI-TP alpha and PI-TP beta used were purified from bovine brain cytosol and covalently labeled with sulfoindocyanine dyes. By this novel method it was found that PI-TP beta was preferentially associated with perinuclear membrane structures whereas PI-TP alpha was predominantly present in the nucleus and in the cytoplasm. This intracellular localization was confirmed by indirect immunofluorescence indicating that the fluorescently labeled PI-TP alpha and PI-TP beta were targeted to the same sites as their endogeneous counterparts.

Animals↗

PubMed2002

Factors affecting interactions between prion protein isoforms.

Interactions between normal, protease-sensitive prion protein (PrP-sen or PrP(C)) and its protease-resistant isoform (PrP-res or PrP(Sc)) are critical in transmissible spongiform encephalopathy (TSE) diseases. To investigate the propagation of PrP-res between cells we tested whether PrP-res in scrapie brain microsomes can induce the conversion of PrP-sen to PrP-res if the PrP-sen is bound to uninfected raft membranes. Surprisingly, no conversion was observed unless the microsomal and raft membranes were fused or PrP-sen was released from raft membranes. These results suggest that the propagation of infection between cells requires transfer of PrP-res into the membranes of the recipient cell. To assess potential cofactors in PrP conversion, we used cell-free PrP conversion assays to show that heparan sulphate can stimulate PrP-res formation, supporting the idea that endogenous sulphated glycosaminoglycans can act as important cofactors or modulators of PrP-res formation in vivo. In an effort to develop therapeutics, the antimalarial drug quinacrine was identified as an inhibitor of PrP-res formation in scrapie-infected cell cultures. Confirmation of the latter result by others has led to the initiation of human clinical trials as a treatment for Creutzfeldt-Jakob disease. PrP-res formation can also be inhibited using a variety of other types of small molecule, specific synthetic PrP peptides, and an antiserum directed at the C-terminus of PrP-sen. The latter results help to localize the sites of interaction between PrP-sen and PrP-res. Disruption of those interactions with antibodies or peptidomimetic drugs may be an attractive therapeutic strategy. The likelihood that PrP-res inhibitors can rid TSE-infected tissues of PrP-res would presumably be enhanced if PrP-res formation were reversible. However, our attempts to measure dissociation of PrP-sen from PrP-res have failed under non-denaturing conditions. Finally, we have attempted to induce the spontaneous conversion of PrP-sen into PrP-res using low concentrations of detergents. A conformational conversion from alpha-helical monomers into high-beta-sheet aggregates and fibrils was induced by low concentrations of the detergent sarkosyl; however, the aggregates had neither infectivity nor the characteristic protease-resistance ofPrP-res.

Animals↗