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Targeted deamination of cytosine bases in DNA by AID/APOBEC-family enzymes is critical for proper immune function, but it also poses risks to genomic integrity. New structures reported by Harris, Aihara and colleagues offer the first glimpses into the enzyme–DNA complex and reveal both expected and unexpected insights into the DNA-binding mode involved in targeting purposeful mutation.
Loss of function of the CFTR anion channel leads to cystic fibrosis, the most common inherited condition in humans of European origin. A recently reported structure for CFTR at 3.7-Å resolution reveals an unexpected 'lasso' domain and provides new insights into channel function in healthy individuals and in people with cystic fibrosis.
Determining the molecular mechanisms responsible for trinucleotide DNA repeat expansions is critical, as such expansions underlie many neuromuscular and neurodegenerative disorders. Mirkin and colleagues now propose that large-scale expansions of trinucleotide repeats can be generated by DNA-break-induced replication.
Little is known about the functions of long noncoding RNAs compared with the amount of accumulated knowledge concerning protein-mediated mechanisms. A report now proposes a novel RNA classification based on similar kinetics of RNA synthesis, processing and turnover, and the authors predict that RNAs within each class might share functional properties.
Warfarin has been the most widely prescribed anticoagulant for decades. It functions by inhibiting the membrane enzyme vitamin K epoxide reductase (VKOR), but the molecular details of this effect have remained elusive. Two new studies shed light on the warfarin-VKOR interaction. The work has implications for precision medicine and could guide drug discovery.
The site of HIV genome integration is likely a contributing factor in viral gene expression, but such context-specific effects are difficult to demonstrate at the population level. A new approach overcomes this obstacle by tracking individual, barcoded viruses to investigate the relationship between integration site location and the corresponding viral transcription, thereby providing insights essential for understanding HIV production, latency and reactivation.
The Eighth International Conference on the Hsp90 Chaperone Machine took place in November 2016 at the Seeon Abbey in Germany. This year's program focused on a variety of topics, reflecting Hsp90's diverse roles in cellular and physiological function. The highlights included structural insights into the Hsp90 folding mechanism and conformational dynamics, post-translational modifications, client protein maturation, Hsp90 cochaperone function and Hsp90's role in disease physiology.
