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Related Concept Videos

Conservation of Protein Domains Over Different Proteins02:26

Conservation of Protein Domains Over Different Proteins

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Protein domains are small structurally independent units that are part of a single amino acid chain.  Although these domains are often structurally independent, they may rely on synergistic effects to perform their functions as part of a larger protein. Protein domains may be conserved within the same organism, as well as across different organisms.
A limited set of protein domains often duplicate and recombine during evolution. These domains can be organized in different combinations to...
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Single-pass Transmembrane Proteins01:25

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Integral membrane proteins are tightly associated with the cell membrane and play a crucial role in cell communication, signaling, adhesion, and transport of the molecules. Some integral membrane proteins are present only in the membrane monolayer. For example, the enzyme fatty acid amide hydrolase is present in the cytoplasmic side of the membrane monolayer. In contrast, another type of integral membrane protein, also known as a transmembrane protein, spans across the membrane. Transmembrane...
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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.
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The rough ER membrane synthesizes, assembles, and embeds transmembrane proteins in diverse topologies. These proteins function as transporters or channels and can remain in the ER membrane or are sent to the Golgi complex, lysosome, and cell membrane.
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Multi-pass Transmembrane Proteins and β-barrels01:09

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In multi-pass transmembrane proteins, the polypeptide chain crosses the membrane more than once. The transmembrane polypeptide chain either forms an α-helix or β-strand structure. α-Helix containing multi-pass transmembrane proteins are ubiquitous, whereas β-strand containing ones are mainly found in gram-negative bacteria, mitochondria, and chloroplasts.
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Transmembrane Domain Oligomerization Propensity determined by ToxR Assay
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Biologically Active Ultra-Simple Proteins Reveal Principles of Transmembrane Domain Interactions.

Ross S Federman1, Anna-Sophia Boguraev2, Erin N Heim2

  • 1Department of Immunobiology, Yale School of Medicine, PO Box 208011, New Haven, CT 06520-8011, USA.

Journal of Molecular Biology
|July 14, 2019
PubMed
Summary

Scientists used simple artificial proteins to understand how transmembrane protein sequences interact. Minor sequence changes significantly altered protein activity, revealing complex activation mechanisms and evolutionary strategies to prevent unwanted interactions.

Keywords:
BPV E5 proteinBaF3 cellserythropoietin receptorhelixtraptamer

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Area of Science:

  • Biochemistry
  • Molecular Biology
  • Protein Engineering

Background:

  • Transmembrane protein interactions are crucial for protein folding and function.
  • The link between transmembrane domain sequences and their functional interactions remains largely unexplored.

Purpose of the Study:

  • To systematically investigate the sequence basis of transmembrane domain interactions using simplified artificial proteins.
  • To understand how specific amino acid sequences within transmembrane domains influence protein function and receptor activation.

Main Methods:

  • Construction and testing of ultra-simple artificial transmembrane proteins, primarily homopolymeric polyleucine.
  • Introduction of single amino acid substitutions to analyze sequence-activity relationships.
  • Assays in cultured mouse cells to measure receptor activation (platelet-derived growth factor β receptor, erythropoietin receptor) and cellular responses (transformation, proliferation).

Main Results:

  • Most artificial polyleucine transmembrane proteins with single substitutions activated target receptors, leading to cell transformation or proliferation.
  • Protein activity showed complex patterns highly sensitive to minor sequence variations in both the artificial protein and the target receptor.
  • The effects of sequence differences were non-additive, indicating intricate molecular mechanisms.
  • Specific leucine residues were essential for activity, with their required positions varying based on the central substituted amino acid.

Conclusions:

  • Ultra-simple artificial proteins can activate target receptors through diverse molecular mechanisms.
  • Sequence diversification in transmembrane domains evolved to minimize off-target interactions.
  • This study provides insights into the fundamental principles governing transmembrane protein interactions and function.