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:
J Virol. 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.
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]
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:
Examples of alpha-glucosidase inhibitors include:
- Acarbose- Precose or Glucobay.
- Miglitol – Glyset.
- Voglibose.
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