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Related Concept Videos

Proteomics01:33

Proteomics

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A proteome is the entire set of proteins that a cell type produces. We can study proteomes using the knowledge of genomes because genes code for mRNAs, and the mRNAs encode proteins. Although mRNA analysis is a step in the right direction, not all mRNAs are translated into proteins.
Proteomics is the study of proteomes' function. It involves the large-scale systematic study of the proteome to denote the protein complement expressed by a genome. Scientist Mark Wilkins coined the term...
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Regulated Protein Degradation02:58

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It is vital to regulate the activity of enzymatic as well as non-enzymatic proteins inside the cell. This can be achieved either through creating a balance between their rate of synthesis and degradation or regulating the intrinsic activity of the protein. Both these regulation mechanisms play an essential role in the normal functioning of cells.
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Covalently Linked Protein Regulators02:04

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Proteins can undergo many types of post-translational modifications, often in response to changes in their environment. These modifications play an important role in the function and stability of these proteins. Covalently linked molecules include functional groups, such as methyl, acetyl, and phosphate groups, and also small proteins, such as ubiquitin. There are around 200 different types of covalent regulators that have been identified.
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The Proteasome01:13

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Eukaryotic cells can degrade proteins through several pathways. One of the most important among these is the ubiquitin-proteasome pathway. It helps the cell eliminate the misfolded, damaged, or unwarranted cytoplasmic proteins in a highly specific manner.
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The Proteasome02:18

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Eukaryotic cells can degrade proteins through several pathways. One of the most important amongst these is the ubiquitin-proteasome pathway. It helps the cell eliminate the misfolded, damaged, or unwarranted cytoplasmic proteins in a highly specific manner.
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Proteins: From Genes to Degradation02:11

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Within a biological system, the DNA encodes the RNA, and the nucleotide sequence in the RNA further defines the amino acid sequence in the protein. This is referred to as “The Central Dogma of Molecular Biology” - a term coined by Francis Crick.  Central dogma is a firm principle in biology that defines the flow of genetic information within any life form. The two fundamental steps in central dogma are - transcription and translation.
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Proteoform-Specific Insights into Cellular Proteome Regulation.

Emma L Norris1, Madeleine J Headlam1, Keyur A Dave1

  • 1From the ‡Protein Discovery Centre and.

Molecular & Cellular Proteomics : MCP
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This study introduces a new proteoform profiling strategy using mass spectrometry to identify and analyze protein variants. The method revealed novel proteoform regulations in cells infected with human respiratory syncytial virus.

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Area of Science:

  • Proteomics
  • Mass Spectrometry
  • Systems Biology

Background:

  • Understanding cellular phenotypes requires knowledge of proteome composition at the proteoform level.
  • Existing methods may not fully capture the diversity of proteoforms.

Purpose of the Study:

  • To develop and exemplify a novel strategy for discovering proteoform-specific information within cellular proteomes.
  • To identify proteoforms, detect proteoform diversity, and discover potential proteoform regulation.

Main Methods:

  • Analysis of bottom-up mass spectrometry data from multiple orthogonal gel electrophoresis (OGE) separations.
  • Fraction-by-fraction analysis with template matching and concordance analysis.
  • Application to human respiratory syncytial virus-infected A549 cells.

Main Results:

  • Successfully identified 10,475 protein profiles with reproducible focusing.
  • Developed a proteoform profiling strategy differentiating proteoforms from alternate splicing and proteolysis.
  • Identified proteoform variations and regulation in response to human respiratory syncytial virus infection, including novel truncated MX1 proteoforms and phosphorylation-driven HSPB1 regulation.

Conclusions:

  • The developed proteoform profiling strategy is effective for identifying proteoforms, detecting diversity, and discovering regulation.
  • The strategy revealed specific proteoform regulations in host cells upon human respiratory syncytial virus infection.
  • This approach is broadly applicable to studying virus-host interactions and other biological systems.