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torsdag 12 mars 2020

Calnexin on S-proteiinin molekulaarinen chaperone endoplasmisessa retikulumissa

https://www.ncbi.nlm.nih.gov/pubmed/22915798
Calnexiini on SARS-2 viruksen chaperoni  endoplasmisessa retikulumissa.  These findings demonstrated that calnexin strictly monitors the maturation of S protein by its direct binding, resulting in conferring infectivity on SARS-CoV.


Solun kalretikuliini/(kalnexiini-sykli proteiinin laadunkontrollijärjestelmässä
.https://www.researchgate.net/publication/23768584_Calreticulin_a_Multi-Process_Calcium-Buffering_Chaperone_of_the_Endoplasmic_Reticulum
Miten  koronaviruksen proteiinit selviävät solun proteiinien laadunkontrollijärjestelmästä ?
 LÄHDE:

2012 Nov;86(21):11745-53. doi: 10.1128/JVI.01250-12. Epub 2012 Aug 22. Monitoring of S protein maturation in the endoplasmic reticulum by calnexin is important for the infectivity of severe acute respiratory syndrome coronavirus.
Fukushi M1, Yoshinaka Y, Matsuoka Y, Hatakeyama S, Ishizaka Y, Kirikae T, Sasazuki T, Miyoshi-Akiyama T. AbstractSevere acute respiratory syndrome coronavirus (SARS-CoV) is the etiological agent of SARS, a fatal pulmonary disorder with no effective treatment. We found that SARS-CoV spike glycoprotein (S protein), a key molecule for viral entry, binds to calnexin, a molecular chaperone in the endoplasmic reticulum (ER), but not to calreticulin, a homolog of calnexin. Calnexin bound to most truncated mutants of S protein, and S protein bound to all mutants of calnexin. Pseudotyped virus carrying S protein (S-pseudovirus) produced by human cells that were treated with small interfering RNA (siRNA) for calnexin expression (calnexin siRNA-treated cells) showed significantly lower infectivity than S-pseudoviruses produced by untreated and control siRNA-treated cells. S-pseudovirus produced by calnexin siRNA-treated cells contained S protein modified with N-glycan side chains differently from other two S proteins and consisted of two kinds of viral particles: those of normal density with little S protein and those of high density with abundant S protein. Treatment with peptide-N-glycosidase F (PNGase F), which removes all types of N-glycan side chains from glycoproteins, eliminated the infectivity of S-pseudovirus.


S-pseudovirus and SARS-CoV produced in the presence of α-glucosidase inhibitors, which disrupt the interaction between calnexin and its substrates, showed significantly lower infectivity than each virus produced in the absence of those compounds.  In S-pseudovirus, the incorporation of S protein into viral particles was obviously inhibited. In SARS-CoV, viral production was obviously inhibited. These findings demonstrated that calnexin strictly monitors the maturation of S protein by its direct binding, resulting in conferring infectivity on SARS-CoV.
PMID:
22915798
PMCID:
PMC3486308
DOI:
10.1128/JVI.01250-12
[Indexed for MEDLINE]
Free PMC Article

lisäys: 
Alpha-glucosidase inhibitors (AGIs) are oral anti-diabetic drugs used for diabetes mellitus type 2 that work by preventing the digestion of carbohydrates (such as starch and table sugar).
Examples of alpha-glucosidase inhibitors include:
  • Acarbose- Precose or Glucobay.
  • Miglitol – Glyset.
  • Voglibose.

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