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Related Concept Videos

Protein Folding Quality Check in the RER01:29

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ER is the primary site for the maturation and folding of soluble and transmembrane secretory proteins. The calnexin cycle is a specific chaperone system that folds and assesses the confirmation of N-glycosylated proteins before they can exit the ER lumen. The primary players of this quality check pipeline are the lectins, ER-resident chaperones, and a glucosyl transferase enzyme. In case the calnexin system in the lumen fails to salvage a misfolded protein, it is transported to the cytoplasm...
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Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
The EGFR can initiate signaling pathways that  lead to cell proliferation, migration, and differentiation. Overexpression of EGFR  stimulates cells to proliferate. Excessive  EGFR...
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Regulation of Nuclear Protein Sorting01:45

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Nuclear protein sorting regulates nucleus composition and gene expression, crucial for determining the fate of a eukaryotic cell. Hence, the entry and exit of molecules across the nuclear envelope is a tightly controlled process. Nuclear protein sorting can be inhibited by one of the following ways: 1) masking cargo signal sequences, 2) modifying the nuclear receptor's affinity for cargo, 3) controlling the nuclear pore size, 4) retaining the cargo during its transit to the cytosol or the...
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During most eukaryotic translation processes, the small 40S ribosome subunit scans an mRNA from its 5' end until it encounters the first start AUG codon. The large 60S ribosomal subunit then joins the smaller one to initiate protein synthesis. The location of the translation initiation is largely determined by the nucleotides near the start codon as there may be multiple translation initiation sites present on the mRNA.  Marilyn Kozak discovered that the sequence RCCAUGG (where R...
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Simple proteins and protein complexes contain only amino acids. In contrast, many other proteins, called conjugated proteins, covalently bond with non-protein moieties.
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Inositol-requiring kinase one or IRE1 is the most conserved eukaryotic unfolded protein response (UPR) receptor. It is a type I transmembrane protein kinase receptor with a distinctive site-specific RNase activity. As the binding mechanics of the misfolded proteins with the N-terminal domain of IRE-1 are unclear, three binding models — direct, indirect, and allosteric -- are proposed for receptor activation. Nevertheless, it is known that once a misfolded protein associates with IRE1, it...
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Calreticulin Regulates SARS-CoV-2 Spike Protein Turnover and Modulates SARS-CoV-2 Infectivity.

Nader Rahimi1, Mitchell R White2,3, Razie Amraei1

  • 1Department of Pathology, School of Medicine, Boston University, Boston, MA 02118, USA.

Cells
|December 9, 2023
PubMed
Summary

Calreticulin (CALR) interacts with the SARS-CoV-2 spike protein, influencing its proteostasis and viral infection. This discovery offers new insights into COVID-19 cardiovascular complications.

Keywords:
COVID-19S-RBDSARS-CoV-2calreticulinendothelial cellsintracellular calcium homeostasisspike protein

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Area of Science:

  • Molecular Biology
  • Virology
  • Cell Biology

Background:

  • Cardiovascular complications are significant in COVID-19.
  • Mechanisms of SARS-CoV-2 endothelial cell infection are not fully understood.

Purpose of the Study:

  • To investigate the interaction between SARS-CoV-2 spike protein and endothelial cells.
  • To identify host factors involved in SARS-CoV-2 infection and proteostasis.

Main Methods:

  • Biochemical analysis to identify S-RBD interacting proteins.
  • Cell treatments with proteasomal and lysosomal inhibitors.
  • shRNA-mediated knockdown of calreticulin (CALR).

Main Results:

  • Calreticulin (CALR) identified as an S-RBD interacting protein via its proline-rich domain.
  • CALR modulates spike protein proteostasis, particularly in lysosome-dependent degradation.
  • CALR knockdown increased SARS-CoV-2 infection and impaired endothelial cell calcium homeostasis.

Conclusions:

  • CALR plays a crucial role in the ER-lysosome-dependent proteolysis of the SARS-CoV-2 spike protein.
  • CALR's function in spike protein degradation and calcium homeostasis is vital for endothelial cell integrity.
  • Findings suggest a link between CALR, SARS-CoV-2 infection, and COVID-19-associated cardiovascular complications.