2,288 research outputs found

    Phase Diagram of alpha-Helical and beta-Sheet Forming Peptides

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    The intrinsic property of proteins to form structural motifs such as alpha-helices and beta-sheets leads to a complex phase behavior in which proteins can assemble into various types of aggregates including crystals, liquidlike phases of unfolded or natively folded proteins, and amyloid fibrils. Here we use a coarse-grained protein model that enables us to perform Monte Carlo simulations for determining the phase diagram of natively folded alpha-helical and unfolded beta-sheet forming peptides. The simulations reveal the existence of various metastable peptide phases. The liquidlike phases are metastable with respect to the fibrillar phases, and there is a hierarchy of metastability

    Direct Visualization of Single Nuclear Pore Complex Proteins Using Genetically-Encoded Probes for DNA-PAINT

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    The nuclear pore complex (NPC) is one of the largest and most complex protein assemblies in the cell and, among other functions, serves as the gatekeeper of nucleocytoplasmic transport. Unraveling its molecular architecture and functioning has been an active research topic for decades with recent cryogenic electron microscopy and super-resolution studies advancing our understanding of the architecture of the NPC complex. However, the specific and direct visualization of single copies of NPC proteins is thus far elusive. Herein, we combine genetically-encoded self-labeling enzymes such as SNAP-tag and HaloTag with DNA-PAINT microscopy. We resolve single copies of nucleoporins in the human Y-complex in three dimensions with a precision of circa 3 nm, enabling studies of multicomponent complexes on the level of single proteins in cells using optical fluorescence microscopy

    Is the Brain Cortex a Fractal?

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    The question is analysed if the human cerebral cortex is self similar in a statistical sense, a property which is usually referred to as being a fractal. The presented analysis includes all spatial scales from the brain size to the ultimate image resolution. Results obtained in two healthy volunteers show that the self similarity does take place down to the spatial scale of 2.5 mm. The obtained fractal dimensions read D=2.73±.05 and D=2.67±.05 correspondingly, which is in good agreement with previously reported results. The new calculational method is volumetric and is based on the fast Fourier Transform of segmented three dimensional high resolved magnetic resonance images. Engagement of FFT enables a simple interpretation of the results and achieves a high performance, which is necessary to analyse the entire cortex

    SPG10 is a rare cause of spastic paraplegia in European families

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    Background: SPG10 is an autosomal dominant form of hereditary spastic paraplegia (HSP), which is caused by mutations in the neural kinesin heavy chain KIF5A gene, the neuronal motor of fast anterograde axonal transport. Only four mutations have been identified to date.Objective: To determine the frequency of SPG10 in European families with HSP and to specify the SPG10 phenotype.Patients and methods: 80 index patients from families with autosomal dominant HSP were investigated for SPG10 mutations by direct sequencing of the KIF5A motor domain. Additionally, the whole gene was sequenced in 20 of these families.Results: Three novel KIF5A mutations were detected in German families, including one missense mutation (c.759G>T, p.K253N), one in frame deletion (c.768_770delCAA, p.N256del) and one splice site mutation (c.217G>A). Onset of gait disturbance varied from infancy to 30 years of age. All patients presented clinically with pure HSP, but a subclinical sensory--motor neuropathy was detected by neurophysiology studies.Conclusions: SPG10 accounts for approximately 3% of European autosomal dominant HSP families. All mutations affect the motor domain of kinesin and thus most likely impair axonal transport. Clinically, SPG10 is characterised by spastic paraplegia with mostly subclinical peripheral neuropathy
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