Unknown

Dataset Information

0

Structural and functional characterization of NEMO cleavage by SARS-CoV-2 3CLpro


ABSTRACT: In addition to its essential role in viral polyprotein processing, the SARS-CoV-2 3C-like (3CLpro) protease can cleave human immune signaling proteins, like NF-κB Essential Modulator (NEMO) and deregulate the host immune response. Here, in vitro assays show that SARS-CoV-2 3CLpro cleaves NEMO with fine-tuned efficiency. Analysis of the 2.14 Å resolution crystal structure of 3CLpro C145S bound to NEMO226–235 reveals subsites that tolerate a range of viral and host substrates through main chain hydrogen bonds while also enforcing specificity using side chain hydrogen bonds and hydrophobic contacts. Machine learning- and physics-based computational methods predict that variation in key binding residues of 3CLpro-NEMO helps explain the high fitness of SARS-CoV-2 in humans. We posit that cleavage of NEMO is an important piece of information to be accounted for in the pathology of COVID-19.

SUBMITTER: Hameedi M 

PROVIDER: S-EPMC8609902 | biostudies-literature |

REPOSITORIES: biostudies-literature

Similar Datasets

| S-EPMC2112940 | biostudies-other
| S-EPMC442122 | biostudies-literature
| S-EPMC7470085 | biostudies-literature
| S-EPMC7395220 | biostudies-literature
| S-EPMC7127318 | biostudies-literature
| S-EPMC8078197 | biostudies-literature
| S-SCDT-EMBOJ-2021-108249 | biostudies-other
| S-EPMC7432786 | biostudies-literature
| S-EPMC8583940 | biostudies-literature