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Related Concept Videos

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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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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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Assembly of the Lipid Bilayer in the ER01:28

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Biological membranes are more than just a barrier separating cell cytoplasm from the outside environment. They are highly dynamic and help maintain the integrity and physiological stability of the cells as well as membrane-bound organelles. Membranes also play vital roles in cell-to-cell and intracellular communication.
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Tail-anchoring of Proteins in the ER Membrane01:45

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Tail-anchored, or TA, proteins are estimated to make up to 3-5% of membrane proteins found in the eukaryotic cell. Such proteins have a single transmembrane domain located approximately 30 amino acid residues upstream from the C-terminal end. As a result, the signal recognition particle (SRP) cannot guide a TA protein to the ER membrane for cotranslational insertion. Hence, they are integrated into the ER membrane post-translationally using their C-terminal end as the anchor. TA proteins...
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Method to Visualize and Analyze Membrane Interacting Proteins by Transmission Electron Microscopy
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Structural basis for membrane insertion by the human ER membrane protein complex.

Tino Pleiner1, Giovani Pinton Tomaleri1, Kurt Januszyk1

  • 1Division of Biology and Biological Engineering, California Institute of Technology, 1200 E. California Ave., Pasadena, CA 91125, USA.

Science (New York, N.Y.)
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Summary
This summary is machine-generated.

The endoplasmic reticulum membrane protein complex (EMC) inserts hydrophobic protein helices into cell membranes. Its structure reveals a hydrophilic pathway and lipid thinning mechanism facilitating this crucial biogenesis step.

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Area of Science:

  • Biochemistry
  • Molecular Biology
  • Structural Biology

Background:

  • Membrane protein biogenesis requires insertion of hydrophobic transmembrane helices into the lipid bilayer.
  • The endoplasmic reticulum (ER) membrane protein complex (EMC) is a conserved insertase crucial for this process.
  • Understanding the EMC's structure and mechanism is vital for deciphering protein insertion pathways.

Purpose of the Study:

  • To determine the high-resolution structure of the human EMC.
  • To elucidate the molecular mechanism by which the EMC facilitates membrane protein insertion.

Main Methods:

  • Cryo-electron microscopy (cryo-EM) of the human EMC in a lipid nanodisc.
  • Atomic model building.
  • Structure-guided mutagenesis.

Main Results:

  • A nearly complete atomic model of the human EMC was determined at 3.4 angstrom resolution.
  • Substrate insertion depends on a methionine-rich cytosolic loop.
  • Insertion occurs through a hydrophilic vestibule formed by EMC3 and EMC6 subunits.
  • The EMC likely utilizes local membrane thinning and a positive charge patch to lower insertion energy.

Conclusions:

  • The EMC employs a unique structural mechanism involving a hydrophilic vestibule and membrane modulation for efficient protein insertion.
  • This study provides atomic-level insights into a fundamental step of membrane protein biogenesis.
  • The findings offer a framework for understanding other membrane protein insertion machineries.