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Related Concept Videos

Translocation of Proteins into the Mitochondria01:19

Translocation of Proteins into the Mitochondria

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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,...
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Structure of Porins01:21

Structure of Porins

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Mitochondria, chloroplasts, and gram-negative bacteria have transmembrane, beta-barrel proteins called porins to mediate the free diffusion of ions and metabolites across the membrane. Mitochondrial porin precursors contain conserved amino acid sequences called beta signals at their C-terminal. Beta signals have a  motif of PoXGXXHyXHy (Po-Polar, X-Any amino acid, G-Glycine, Hy-LargeHydrophobic), which are crucial for precursor recognition to initiate precursor assembly. Beta-barrel...
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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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Mitochondrial Protein Sorting01:39

Mitochondrial Protein Sorting

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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.
Most of these mitochondrial proteins are encoded by the nucleus and imported to the mitochondria as unfolded or loosely folded precursors. Mitochondrial precursors...
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Energy to Drive Translocation01:37

Energy to Drive Translocation

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Mitochondrial protein import is powered by two distinct energy sources: ATP hydrolysis and electrochemical potential across the inner membrane. Newly synthesized precursors are bound by cytosolic chaperones of the Hsp70 family, which guide them to the import receptors on the mitochondrial surface. Utilizing the energy of ATP hydrolysis, Hsp70 chaperones transfer these precursors to the TOM receptors on the mitochondrial outer membrane.
Generally, polypeptides are unfolded by two distinct...
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Protein Translocation Machinery on the ER Membrane01:28

Protein Translocation Machinery on the ER Membrane

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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...
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Related Experiment Video

Updated: Mar 6, 2026

Quantitative Methods to Study Protein Arginine Methyltransferase 1-9 Activity in Cells
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The Structure and Function of the PRMT5:MEP50 Complex.

Stephen Antonysamy1

  • 1Structural Biology, Discovery Chemistry Research and Technologies, Eli Lilly and Company, Lilly Biotechnology Center, 10290 Campus Point Drive, San Diego, CA, 92121, USA. antonysamyst@lilly.com.

Sub-Cellular Biochemistry
|March 9, 2017
PubMed
Summary

Protein arginine methyltransferase 5 (PRMT5) is crucial in cell cycle processes and is overexpressed in cancers. Understanding its structure offers insights for developing PRMT5 as a drug target.

Keywords:
DevelopmentEpigeneticsMEP50MethyltransferasesPPIPRMT5WD40 domain

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Related Experiment Videos

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Area of Science:

  • Biochemistry
  • Molecular Biology
  • Cancer Biology

Background:

  • Protein arginine methyltransferase 5 (PRMT5) is a key enzyme involved in cellular processes and cell cycle regulation.
  • PRMT5 functions in a complex with MEP50/p44/WDR77, catalyzing symmetric dimethylation of arginine residues on target proteins.
  • Aberrant PRMT5 expression is linked to various cancers, highlighting its potential as a therapeutic target.

Purpose of the Study:

  • To elucidate the structural basis of PRMT5 function.
  • To provide insights into the mechanism of PRMT5-mediated arginine methylation.
  • To facilitate the rational design of PRMT5-targeted cancer therapies.

Main Methods:

  • X-ray crystallography was employed to determine the structure of the PRMT5:MEP50 complex.
  • The complex was crystallized in the presence of an S-adenosylmethionine analog and a substrate peptide.

Main Results:

  • The study determined the high-resolution structure of the 453 kDa heterooctameric PRMT5:MEP50 complex.
  • The structure reveals the binding sites for the S-adenosylmethionine analog and the substrate peptide.
  • Structural insights into the catalytic mechanism and substrate recognition of PRMT5 were obtained.

Conclusions:

  • The determined structure of the PRMT5:MEP50 complex provides a detailed molecular understanding of its function.
  • This structural information is valuable for the development of novel inhibitors targeting PRMT5 in cancer treatment.
  • The findings pave the way for structure-based drug design against PRMT5.