Biology subjects

zhang, c.

Publications and source records attributed to zhang, c..

2 recordsLinked to original sources

bioRxiv2024

IP3R1 is required for meiotic progression and embryonic development by regulating mitochondrial calcium and oxidative damage

Calcium ions (Ca2+) regulate cell proliferation and differentiation and participate in various physiological activities of cells. The calcium transfer protein inositol 1,4,5-triphosphate receptor (IP3R), located between the endoplasmic reticulum (ER) and mitochondria, plays an important role in regulating Ca2+ levels. However, the mechanism by which IP3R1 affects porcine meiotic progression and embryonic development remains unclear. We established a model in porcine oocytes using siRNA-mediated knockdown of IP3R1 to investigate the effects of IP3R1 on porcine oocyte meiotic progression and embryonic development. The results indicated that a decrease in IP3R1 expression significantly enhanced the interaction between the ER and mitochondria. Additionally, the interaction between the ER and the mitochondrial Ca2+ ([Ca2+]m) transport network protein IP3R1-GRP75-VDAC1 was disrupted. PLA decreased IP3R1, weakened the pairwise interaction between IP3R1-GRP75 and VDAC1 and significantly enhanced the interaction between GRP75 and VDAC1, resulting in the accumulation of large amounts of [Ca2+]m. These changes led to mitochondrial oxidative stress and reduced ATP production, which hindered the maturation and late development of porcine oocytes and caused apoptosis.

cell biology↗

bioRxiv2023

Structural basis for the concerted antiphage activity in the SIR2-HerA system

Recently, a novel two-gene bacterial defense system against phages, encoding a SIR2 NADase and a HerA translocase, has been identified. However, the molecular mechanism of the bacterial SIR2-HerA immune system remains unclear. Here, we determine the cryo-EM structures of SIR2, HerA and their complex in different functional states. The SIR2 proteins oligomerize into a dodecameric ring-shaped structure consisting of two layers of interlocked hexamers, in which each SIR2 unit exhibits an auto-inhibited conformation. Distinct from the canonical AAA+ proteins, the HerA hexamer in this antiphage system adopts a split spiral arrangement, resembling the substrate-binding state, which is stabilized by a unique C-terminal extension. SIR2 and HerA proteins assemble into a [~] 1.1 MDa torch-shaped complex to fight against phage infection. Importantly, disruption of the interactions between SIR2 and HerA largely abolishes the antiphage activity. Interestingly, HerA binding alters the oligomer state of SIR2, switching from a 12-mer state to a 14-mer state. On the other hand, binding of SIR2 stimulates the ATPase activity of HerA. Together, our study not only provides a structural basis for the functional communications between SIR2 and HerA proteins, but also unravels a novel concerted antiviral mechanism through nucleotide (NAD+ and ATP) depletion.

biochemistry↗