Question

In: Anatomy and Physiology

2. Describe the mechanism of targeting of proteins to the secretory pathway. Be sure to provide...

2. Describe the mechanism of targeting of proteins to the secretory pathway. Be sure to provide the step-by-step molecular mechanism of entry of proteins into the ER.

3. Outline an experimental progression involving site-directed mutagenesis to test the hypothesis that basic (positive) amino acids are important for opening a voltage gated ion channel.

Part 2 1. Discuss the difference between a genomic and cDNA library. Give details with respect to the preparation techniques.

Solutions

Expert Solution

Ans 2. The secretory pathway refers to the ER(Endoplasmic reticulum), Golgi Apparatus, and the vesicles that travel in between them as well as the cell membrane.

It’s named ‘secretory’ for being the pathway by which the cell secretes proteins into the extracellular environment.

  • This pathway also processes proteins that will be membrane-bound (whether in the cellular membrane or in the ER or Golgi membranes themselves), as well as lysosomal enzymes, and also any proteins that will live their lives in the secretory pathway itself.
  • It is responsible for the processing of proteins for export from the cell.
  • The synthesis of all proteins begins in the cytosol compartment.
  • For proteins entering the secretory pathway, the first step is targeting to the endoplasmic reticulum.

Co-translational translocation.

  • Synthesis of proteins entering the endoplasmic reticulum is initiated on free ribosomes.
  • A targeting sequence of hydrophobic amino acids near the amino-terminal end of the growing polypeptide results in the binding of the ribosome to the ER membrane and in the insertion of the polypeptide into the endoplasmic reticulum.
  • Targeting to the endoplasmic reticulum begins with a special sequence at the very N-terminus, the beginning of the protein, which tends to be somewhat apolar or hydrophobic this signal peptide sequence (a sequence of at least eight hydrophobic amino acids at the amino-terminal end of the polypeptide) draws a Signal recognition particle(SRP) while the protein is still being synthesized on the ribosome.
  • This greatly reduces the rate of translocation and allows the ribosome to attach to the endoplasm reticulum by means of a special SRP receptor in the ER membrane.
  • The ribosome becomes attached to a ribosome receptor that also functions as a translocation channel for the newly synthesized polypeptide
  • The synthesis pauses while the ribosome-protein complex is transferred to an SRP receptor on the ER.
  • As the ribosome becomes attached, the SRP is removed and translation resumes.
  • The nascent protein is then inserted into the translocon, a membrane-bound protein conducting channel composed of the Sec61 translocation complex.
  • In secretory proteins and type, I transmembrane protein the signal sequence is immediately cleaved from the nascent polypeptide once it has been translocated into the membrane of the ER.
  • The signal sequence of type II membrane proteins and some polytopic membrane proteins are not cleaved off and therefore are referred to as signal anchor sequences.
  • Within the ER, the protein is first covered by a chaperone protein to protect it from the high concentration of other proteins in the ER, giving it time to fold correctly inside the lumen of the ER.
  • Once folded the protein is modified as needed then transported to the Golgi for further processing and goes to its target organelles or is retained in the ER by various ER retention mechanisms.

Post-translational translocation

  • Most secretory proteins use the above pathway to enter the ER, but some proteins are translated into the cytosol and then later transported to ER.

This way the proteins are targetted to the secretory pathway.


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