Glioblastoma multiforme (GBM) is a clinically and pathologically heterogeneous brain tumor. Previous studies of transcriptional profiling have revealed biologically relevant GBM subtypes associated with specific mutations and dysregulated pathways. Here, we applied a modified proteome to uncover abnormal protein expression profile in a MRI-classified group I GBM (GBM1), which has a spatial relationship with one of the adult neural stem cell niches, subventricular zone (SVZ). Most importantly, we identified molecular characteristics in this type of GBM that include up-regulation of metabolic enzymes, ribosomal proteins, and heat shock proteins. As GBM1 often recurs at great distances from the initial lesion, the rewiring of metabolism, and ribosomal biogenesis may facilitate cancer cells’ growth and survival during tumor progression. The intimate contact between GBM1 and the SVZ raises the possibility that tumor cells in GBM1 may be most related to SVZ cells. In support of this notion, we found that markers representing SVZ cells are highly expressed in GBM1. Emerged findings from our study provide a specific protein expression profile in GBM1 and offer better prediction or therapeutic implication for this multifocal GBM.
Many eukaryotic proteins are predicted to be intrinsically disordered meaning that they lack stable secondary and tertiary structure. Such intrinsically disordered proteins (IDPs) are extremely flexible and exhibit large conformational fluctuations in their native state. Despite lacking the ''lock and key'' interfaces
Intrinsically disordered proteins (IDPs) do not possess well-defined three-dimensional structures in solution under physiological conditions. We develop all-atom, united-atom, and coarse-grained Langevin dynamics simulations for the IDP a-synuclein that include geometric, attractive hydrophobic, and screened electrostatic interactions and are calibrated to the inter-residue separations measured in recent smFRET experiments. We find that a-synuclein is disordered with conformational statistics that are intermediate between random walk and collapsed globule behavior and demonstrate close resemblance to the known experimental data. We use these simulations to study oligomerization and aggregation of multiple a-synuclein proteins that may precede amyloid formation.
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