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Related Concept Videos

Overview of Protein Sorting and Transport01:45

Overview of Protein Sorting and Transport

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Eukaryotic cells have different membrane-bound organelles with distinct protein requirements. The process by which proteins are targeted to a specific organelle is called protein sorting.
Protein sorting can be of two types: signal-based sorting and vesicle-based trafficking. In signal-based sorting, specific amino acid sequences called sorting signals target proteins to the proper location inside the cell either via gated transport or by protein translocation.  In gated transport, folded...
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Protein Transport into the Inner Mitochondrial Membrane01:34

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Nuclear encoded mitochondrial precursors are imported to the inner membrane in a multistep process involving two separate translocons, TIM22 and TIM23. TIM23 is a cation-selective pore that remains closed by the N terminal segment of the protein. Negative charges on the TIM23 act as a receptor for the incoming precursor, pulling the positively charged matrix-targeting sequence for peptide insertion and translocation.
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Bacterial Translocation and Protein Secretion01:26

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Bacterial protein secretion involves translocation systems to ensure proteins reach their designated locations, including the plasma membrane, periplasm, outer membrane, or the external environment. These translocation systems are vital for bacterial physiology, supporting processes like membrane assembly, enzymatic activity in the periplasm, and interactions with the external environment. The division of labor between Sec and Tat pathways ensures efficiency in handling proteins with diverse...
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Cotranslational Protein Translocation01:20

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Translocation of proteins across membranes is an ancient process that occurs even in bacteria and archaebacteria. In fact, the components of the translocation machinery are still conserved between prokaryotes and eukaryotes.
Sec61 channel partners for cotranslational translocation
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Mitochondria are double-membrane organelles of the eukaryotes involved in cellular metabolism, signaling, ATP synthesis, and programmed cell death.  Each of these processes requires specific proteins and enzymes that must be correctly sorted to the right mitochondrial subcompartment for the proper functioning of the organelle.
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Carrier-mediated transport is a pivotal process in drug absorption, particularly for lipid-insoluble drugs, and encompasses facilitated diffusion and active transport. Facilitated diffusion allows drugs to move along their concentration gradient without energy expenditure, while active transport utilizes ATP to drive drug movement against this gradient.
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Related Experiment Video

Updated: Mar 15, 2026

Delivery of Proteins, Peptides or Cell-impermeable Small Molecules into Live Cells by Incubation with the Endosomolytic Reagent dfTAT
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Delivery of Proteins, Peptides or Cell-impermeable Small Molecules into Live Cells by Incubation with the Endosomolytic Reagent dfTAT

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Efficient Mini-Transporter for Cytosolic Protein Delivery.

Ning Zhang1, Ziqiang Yan1, Xue Zhao1

  • 1CAS Key Laboratory of Soft Matter Chemistry, iChEM (Collaborative Innovation Center of Chemistry for Energy Materials), Department of Chemistry, University of Science and Technology of China , Hefei, Anhui 230026, P. R. China.

ACS Applied Materials & Interfaces
|September 16, 2016
PubMed
Summary

Researchers developed a novel dendritic molecule, TG6, for efficient protein delivery into cells. This serum-stable and low-toxic transporter preserves protein function, advancing protein-based therapeutics.

Keywords:
cell penetrating peptidescytosolic deliveryguanidiniumprotein deliverystructure design

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Area of Science:

  • Biotechnology
  • Drug Delivery
  • Molecular Biology

Background:

  • Efficient cytosolic delivery of active proteins is crucial for developing advanced protein-based therapeutics.
  • Arginine-rich cell-penetrating peptides (RPPs) are widely studied for intracellular delivery but require improvements in efficiency, serum stability, and cytotoxicity.
  • Synthetic analogs of RPPs offer a promising alternative for enhanced cytosolic protein delivery.

Purpose of the Study:

  • To design and synthesize a novel molecular transporter for efficient intracellular protein delivery.
  • To evaluate the efficacy, serum stability, and cytotoxicity of the designed transporter.
  • To demonstrate the preservation of protein structure and function after conjugation and delivery.

Main Methods:

  • Design and synthesis of a dendritic small molecule (TG6) with a rigid core and flexible arms bearing guanidinium groups.
  • Conjugation of TG6 with proteins.
  • Assessment of cellular uptake and cytosolic delivery of TG6-protein conjugates.
  • Evaluation of protein structure and function preservation post-delivery.
  • In vitro assessment of serum stability and cytotoxicity.

Main Results:

  • The synthesized dendritic molecule TG6 effectively delivers proteins into the cytosol.
  • TG6-protein conjugates maintain the native structure and biological activity of the proteins.
  • TG6 exhibits excellent serum stability and low cytotoxicity.
  • TG6 demonstrates efficient delivery of both small molecules and large active proteins.

Conclusions:

  • The dendritic small molecule TG6 is a highly effective and safe molecular transporter for cytosolic protein delivery.
  • TG6 overcomes limitations of traditional RPPs, offering improved serum stability and reduced toxicity.
  • This novel transporter holds significant potential for advancing protein-based therapeutics and biotechnological applications.