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Related Concept Videos

Mitochondrial Precursor Proteins01:39

Mitochondrial Precursor Proteins

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 precursors...
Translocation of Proteins into the Mitochondria01:19

Translocation of Proteins into the Mitochondria

Mitochondrial precursors are translocated to the internal subcompartments via independent mechanisms involving distinct protein machineries called translocases.
Sorting of outer membrane proteins:
Mitochondrial outer membrane proteins are of two types: the transmembrane, beta-barrel porins, and the membrane-anchored, alpha-helical proteins. Beta-barrel porin precursors are translocated by the TOM complex and inserted into the outer mitochondrial membrane by the SAM complex. In contrast,...
Protein Transport into the Inner Mitochondrial Membrane01:34

Protein Transport into the Inner Mitochondrial Membrane

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.
Transport of mitochondrial precursors across the TIM23 channel is driven by...
Insertion of Single-pass Transmembrane Proteins in the RER01:26

Insertion of Single-pass Transmembrane Proteins in the RER

Integral membrane proteins are proteins adhered to the lipid bilayer of a cell organelle or membrane. They can be of two types: transmembrane integral proteins that span the lipid bilayer and monotopic proteins that are attached to either side of the membrane but do not pass through it.
Integral transmembrane proteins possess transmembrane and extra membrane domains. The transmembrane domains are primarily made of 20-25 hydrophobic amino acids arranged in a helical secondary confirmation. These...
Protein Translocation Machinery on the ER Membrane01:28

Protein Translocation Machinery on the ER Membrane

The translocon complex situated on the ER membrane is the main gateway for the protein secretory pathway. It facilitates the transport of nascent peptides into the ER lumen and their insertion into the ER membrane.
Sec61 protein conducting channel
In eukaryotes, the translocon complex comprises a core heterotrimeric translocator channel called the Sec61 complex. This channel includes three transmembrane proteins, Sec61α, Sec61β, and Sec61γ, and is the largest subunit of the translocon complex.
Porin Insertion in the Outer Mitochondrial Membrane01:12

Porin Insertion in the Outer Mitochondrial Membrane

Porins are beta-barrel proteins translocated to the mitochondrial outer membrane through the TOM complex into the intermembrane space. Porin precursors bind TIM chaperones within the intermembrane space and are guided to the Sorting and Assembly Machinery complex or SAM complex on the outer mitochondrial membrane.
Three models describe the assembly of porins by the SAM complex and their insertion into the outer membrane. Model 1 suggests that porins are assembled outside the SAM channel as the...

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Related Experiment Video

Updated: Jun 5, 2026

Analysis of Transforming Growth Factor &#223; Family Cleavage Products Secreted Into the Blastocoele of Xenopus laevis Embryos
06:57

Analysis of Transforming Growth Factor ß Family Cleavage Products Secreted Into the Blastocoele of Xenopus laevis Embryos

Published on: July 21, 2021

Proprotein convertases process Pmel17 during secretion.

Ralf M Leonhardt1, Nathalie Vigneron, Christoph Rahner

  • 1Department of Immunobiology, Yale University School of Medicine, New Haven, Connecticut 06519, USA. Ralf.Leonhardt@yale.edu

The Journal of Biological Chemistry
|January 21, 2011
PubMed
Summary
This summary is machine-generated.

Pmel17 processing occurs during secretion, not in melanosomes, challenging current models of melanocyte protein maturation. This early cleavage primes Pmel17 for its functional role in melanin deposition.

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Demonstration of Proteolytic Activation of the Epithelial Sodium Channel (ENaC) by Combining Current Measurements with Detection of Cleavage Fragments
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Demonstration of Proteolytic Activation of the Epithelial Sodium Channel (ENaC) by Combining Current Measurements with Detection of Cleavage Fragments

Published on: July 5, 2014

Optimized Protocol for the Extraction of Proteins from the Human Mitral Valve
09:13

Optimized Protocol for the Extraction of Proteins from the Human Mitral Valve

Published on: June 14, 2017

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Last Updated: Jun 5, 2026

Analysis of Transforming Growth Factor &#223; Family Cleavage Products Secreted Into the Blastocoele of Xenopus laevis Embryos
06:57

Analysis of Transforming Growth Factor ß Family Cleavage Products Secreted Into the Blastocoele of Xenopus laevis Embryos

Published on: July 21, 2021

Demonstration of Proteolytic Activation of the Epithelial Sodium Channel (ENaC) by Combining Current Measurements with Detection of Cleavage Fragments
08:56

Demonstration of Proteolytic Activation of the Epithelial Sodium Channel (ENaC) by Combining Current Measurements with Detection of Cleavage Fragments

Published on: July 5, 2014

Optimized Protocol for the Extraction of Proteins from the Human Mitral Valve
09:13

Optimized Protocol for the Extraction of Proteins from the Human Mitral Valve

Published on: June 14, 2017

Area of Science:

  • Cell Biology
  • Biochemistry
  • Melanogenesis Research

Background:

  • Pmel17 is a key protein in melanocytes and melanoma, forming a matrix for melanin deposition within melanosomes.
  • Proprotein convertases (PCs) cleave Pmel17 into smaller fragments, a process critical for its function.
  • The exact location of Pmel17 processing has been debated, with the prevailing model suggesting it occurs within melanosomes.

Purpose of the Study:

  • To investigate the precise cellular location and kinetics of Pmel17 processing by proprotein convertases.
  • To challenge and refine the existing model of Pmel17 maturation and trafficking.
  • To determine if Pmel17 processing is dependent on its entry into the endocytic pathway.

Main Methods:

  • Comparative analysis of wild-type Pmel17 and a secreted soluble Pmel17 derivative.
  • Assessment of processing kinetics under secretion-inhibiting conditions (monensin).
  • Evaluation of newly synthesized surface Pmel17 cleavage.
  • Analysis of Pmel17's unconventional cleavage motif.

Main Results:

  • Pmel17 processing occurs during the secretion pathway, independent of melanosome entry.
  • Processing is efficient and occurs even with secretion inhibitors, indicating Pmel17 is a highly effective substrate.
  • Newly synthesized surface Pmel17 is already fully cleaved.
  • Pmel17 function is not dependent on the specific identity of its cleavage motif, even with an unconventional P4-position sequence.

Conclusions:

  • The current model of Pmel17 maturation requires revision; processing initiates early during secretion.
  • This early cleavage event primes Pmel17 for subsequent functional processing steps.
  • Pmel17 processing is a rapid and efficient event occurring co-translationally or during transit.