In tailed bacteriophages and herpes viruses, the viral DNA is packaged through the portal protein channel. Channel closure is essential to prevent DNA release after packaging. Here we present the connector structure from bacteriophage SPP1 using cryo-electron microscopy and single particle analysis. The multiprotein complex comprises the portal protein gp6 and the head completion proteins gp15 and gp16. Although we show that gp6 in the connector has a fold similar to that of the isolated portal protein, we observe conformational changes in the region of gp6 exposed to the DNA-packaging ATPase and to gp15. This reorganization does not cause closure of the channel. The connector channel traverses the full height of gp6 and gp15, but it is closed by gp16 at the bottom of the complex. Gp16 acts as a valve whose closure prevents DNA leakage, while its opening is required for DNA release upon interaction of the virus with its host.
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http://dx.doi.org/10.1093/emboj/cdg123 | DOI Listing |
Background: Plasma biomarkers have emerged as a promising tool to detect the presence of Alzheimer's disease (AD) when cognitive symptoms have not yet emerged. However, there is also a pressing need to detect and track subtle cognitive change at the preclinical stage of AD for population screening purposes and to monitor disease progression at scale. A potential solution is remote cognitive assessment, yet it is still not extensively employed.
View Article and Find Full Text PDFBackground: Early adversity has been reported as a risk factor for dementia. Adverse maternal control (MC) during childhood is believed to impact neural developmental pathways. Here we studied the associations between adverse MC and the volume of the dorsal striatum in older adults given evidence from the childhood adversity literature of structural reductions and altered reward processing.
View Article and Find Full Text PDFBackground: There is an urgent need for new therapeutic and diagnostic targets for Alzheimer's disease (AD). Dementia afflicts roughly 55 million individuals worldwide, and the prevalence is increasing with longer lifespans and the absence of preventive therapies. Given the demonstrated heterogeneity of Alzheimer's disease in biological and genetic components, it is critical to identify new therapeutic approaches.
View Article and Find Full Text PDFBackground: Although investment in biomedical and pharmaceutical research has increased significantly over the past two decades, there are no oral disease-modifying treatments for Alzheimer's disease (AD).
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Alzheimers Dement
December 2024
Indiana University School of Medicine, Indianapolis, IN, USA.
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