A Resident State Allows Influenza Polymerase to Smoothly Switch between Transcription and Replication Cycles

Influenza polymerase (FluPol) transcripts viral mRNA and switches to replicate viral genome after transcription. However, it remains unknown how FluPol switches between transcription and replication cycles, especially when considering that the structural basis of these two functions is fundamentally different. Here, we proposed a mechanism that FluPol achieves the functional switching between these two cycles through an unreported intermediate conformation, termed as resident state. We obtained a resident state structure of H5N1 FluPol at 3.7 angstroms using cryo-EM, which is characterized by a blocked Cap-binding domain and a contracted core region, distinct from the structures of either transcription or replication states. Structural analysis results suggest that the resident state structure is feasible to smoothly transit into structures of both transcription and replication states. Furthermore, we show that formation of the resident state is required for both transcription and replication activities of FluPol. Together, the transcription and replication cycles of FluPol are connected via a resident state.

Functional Switching of a Native Neuropeptide Through Interactions with Pathogenic Factors in Dementia

We discovered that the function of a native neuropeptide, somatostatin (SST), is switched through its conformational transition in the presence of metal ions, metal-free amyloid-beta (Abeta), and metal-bound Abeta that are associated with toxicity observed in the brains of Alzheimer’s disease patients.

Functional Switching of a Native Neuropeptide Through Interactions with Pathogenic Factors in Dementia

We discovered that the function of a native neuropeptide, somatostatin (SST), is switched through its conformational transition in the presence of metal ions, metal-free amyloid-beta (Abeta), and metal-bound Abeta that are associated with toxicity observed in the brains of Alzheimer’s disease patients.

A biological switching valve evolved in the female of a sex-role reversed cave insect to receive multiple seminal packages

We report a functional switching valve within the female genitalia of the Brazilian cave insect Neotrogla. The valve complex is composed of two plate-like sclerites, a closure element, and in-and-outflow canals. Females have a penis-like intromittent organ to coercively anchor males and obtain voluminous semen. The semen is packed in a capsule, whose formation is initiated by seminal injection. It is not only used for fertilization but also consumed by the female as nutrition. The valve complex has two slots for insemination so that Neotrogla can continue mating while the first slot is occupied. In conjunction with the female penis, this switching valve is a morphological novelty enabling females to compete for seminal gifts in their nutrient-poor cave habitats through long copulation times and multiple seminal injections. The evolution of this switching valve may have been a prerequisite for the reversal of the intromittent organ in Neotrogla.