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Mitochondrial Precursor Proteins01:39

Mitochondrial Precursor Proteins

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Mitochondrial precursors are partially unfolded or loosely folded polypeptide chains. Newly synthesized precursors are inhibited from spontaneously folding into their native conformation by the cytosolic chaperones, heat shock proteins 70 (Hsp70), and mitochondrial import stimulation factors (MSFs). Precursors bound to MSFs are guided to the TOM70-TOM37 receptors, while precursors bound to Hsp70  chaperones are targetted to TOM20-TOM22 receptor complexes.
Most of the mitochondrial...
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Lysosomal Hydrolases01:22

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Lysosomes are the site for the degradation of macromolecules and biological polymers released during membrane trafficking events such as secretory, endocytic, autophagic, and phagocytic pathways. The membrane-enclosed area of the lysosome, called the lumen, contains hydrolytic enzymes active in an acidic environment. These acid hydrolases are functional at a pH between 4.5 and 5 and are involved in cellular processes such as cell signaling, energy metabolism, restoration of the plasma membrane,...
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Tail-anchoring of Proteins in the ER Membrane01:45

Tail-anchoring of Proteins in the ER Membrane

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Tail-anchored, or TA, proteins are estimated to make up to 3-5% of membrane proteins found in the eukaryotic cell. Such proteins have a single transmembrane domain located approximately 30 amino acid residues upstream from the C-terminal end. As a result, the signal recognition particle (SRP) cannot guide a TA protein to the ER membrane for cotranslational insertion. Hence, they are integrated into the ER membrane post-translationally using their C-terminal end as the anchor. TA proteins...
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Leaky Scanning02:28

Leaky Scanning

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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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Receptor-mediated Endocytosis01:20

Receptor-mediated Endocytosis

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Receptor-mediated endocytosis is when bulk amounts of specific molecules are imported into a cell after binding to cell surface receptors. The molecules bound to these receptors are taken into the cell through inward folding of the cell surface membrane, which is eventually pinched off into a vesicle within the cell. Structural proteins, such as clathrin, coat the budding vesicle.
Clathrin-Mediated Endocytosis of LDL
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Receptor-mediated Endocytosis01:38

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Related Experiment Video

Updated: Apr 30, 2026

A Fluorogenic Peptide Cleavage Assay to Screen for Proteolytic Activity: Applications for coronavirus spike protein activation
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A Fluorogenic Peptide Cleavage Assay to Screen for Proteolytic Activity: Applications for coronavirus spike protein activation

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Membrane ectopeptidases targeted by human coronaviruses.

Berend Jan Bosch1, Saskia L Smits2, Bart L Haagmans2

  • 1Virology Division, Department of Infectious Diseases & Immunology, Faculty of Veterinary Medicine, Utrecht University, 3508 TD Utrecht, the Netherlands.

Current Opinion in Virology
|April 26, 2014
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Summary

Six coronaviruses infect the human respiratory tract by interacting with cell receptors. Three key ectopeptidases—DPP4, ACE2, and APN—serve as entry points for coronaviruses, potentially amplifying host responses.

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Area of Science:

  • Virology
  • Molecular Biology
  • Cell Biology

Background:

  • Six human coronaviruses cause respiratory illness, ranging from mild to severe.
  • Viral entry into host cells requires interaction with specific cellular receptors.
  • Understanding these interactions is crucial for developing antiviral strategies.

Purpose of the Study:

  • To identify and characterize the host cell receptors used by human-infecting coronaviruses.
  • To investigate the role of host proteases in facilitating coronavirus entry.
  • To explore the implications of receptor conservation for interspecies transmission and disease severity.

Main Methods:

  • Bioinformatic analysis of known coronavirus-receptor interactions.
  • In vitro studies to confirm receptor binding and viral entry.
  • Comparative analysis of receptor expression across different host species.

Main Results:

  • Identified dipeptidyl peptidase 4 (DPP4), angiotensin-converting enzyme 2 (ACE2), and aminopeptidase N (APN) as key entry receptors for four human coronaviruses.
  • Demonstrated that enzymatic activity of these receptors is not essential for viral entry.
  • Showed that co-expression of host proteases enhances viral entry efficiency.
  • Highlighted the evolutionary conservation of these receptors, suggesting potential for zoonotic transmission.

Conclusions:

  • DPP4, ACE2, and APN are critical host factors for human coronavirus infections.
  • Host proteases play a significant role in modulating viral entry and infectivity.
  • The conserved nature of these receptors poses a risk for interspecies coronavirus transmission and potential pandemics.
  • Dysregulation of these peptidase systems may exacerbate respiratory distress during infection.