Biology subjects

Murata, D.

Publications and source records attributed to Murata, D..

2 recordsLinked to original sources

bioRxiv2024

Caspase cleavage of Influenza A virus M2 disrupts M2-LC3 interaction and regulates virion production

Influenza A virus (IAV) Matrix 2 (M2) protein is an ion channel, required for efficient viral entry and egress. M2 interacts with the small ubiquitin-like LC3 protein through a cytoplasmic C-terminal LC3 interacting region (LIR). Here, we report that M2 is cleaved by caspases, abolishing the M2-LC3 interaction. A crystal structure of the M2 LIR in complex with LC3 indicates the caspase cleavage tetrapeptide motif (82SAVD85) is an unstructured linear motif that does not overlap with the LIR. Furthermore, an IAV mutant expressing a permanently truncated M2, mimicking caspase cleavage, is impaired in M2 plasma membrane transport and produces a significantly attenuated virus. Our results reveal a dynamic regulation of the M2-LC3 interaction by caspases. This highlights the role of host proteases in regulating IAV exit, relating virion production with host cell state.

microbiology↗

bioRxiv2022

Role of human HSPE1 for OPA1 processing independent of HSPD1

The mtHSP60/HSPD1-mtHSP10/HSPE1 system prevents protein misfolding and maintains proteostasis in the mitochondrial matrix. Altered activities of this chaperonin system have been implicated in human diseases, such as cancer and neurodegeneration. However, how defects in HSPD1 and HSPE1 affect mitochondrial structure and dynamics remains elusive. In the current study, we address this fundamental question in a human cell line, HEK293T. We found that the depletion of HSPD1 or HSPE1 results in fragmentation of mitochondria, suggesting a decrease in mitochondrial fusion. Supporting this notion, HSPE1 depletion led to proteolytic inactivation of OPA1, a dynamin-related GTPase that fuses the mitochondrial membrane. This OPA1 inactivation was mediated by a stress-activated metalloprotease, OMA1. In contrast, HSPD1 depletion did not induce OMA1 activation or OPA1 cleavage. These data suggest that HSPE1 controls mitochondrial morphology through a mechanism separate from its chaperonin activity.

cell biology↗