MIA40 has a key role in oxidative protein folding in the mitochondrial intermembrane space. We present the solution structure of human MIA40 and its mechanism as a catalyst of oxidative folding. MIA40 has a 66-residue folded domain made of an alpha-helical hairpin core stabilized by two structural disulfides and a rigid N-terminal lid, with a characteristic CPC motif that can donate its disulfide bond to substrates. The CPC active site is solvent-accessible and sits adjacent to a hydrophobic cleft. Its second cysteine (Cys55) is essential in vivo and is crucial for mixed disulfide formation with the substrate. The hydrophobic cleft functions as a substrate binding domain, and mutations of this domain are lethal in vivo and abrogate binding in vitro. MIA40 represents a thioredoxin-unrelated, minimal oxidoreductase, with a facile CPC redox active site that ensures its catalytic function in oxidative folding in mitochondria.
There is an urgent need to understand the behavior of the novel coronavirus
(SARS-COV-2), which is the causative agent of COVID-19, and to develop point-of-care
diagnostics. Here, a glyconanoparticle platform is used to discover that
N
-acetyl neuraminic acid has affinity toward the SARS-COV-2 spike
glycoprotein, demonstrating its glycan-binding function. Optimization of the particle
size and coating enabled detection of the spike glycoprotein in lateral flow and showed
selectivity over the SARS-COV-1 spike protein. Using a virus-like particle and a
pseudotyped lentivirus model, paper-based lateral flow detection was demonstrated in
under 30 min, showing the potential of this system as a low-cost detection platform.
A nine-residue intermembrane-targeting signal brings the active Cys of substrate proteins into contact with Mia40 oxidase for folding and import into mitochondria.
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