GR

Moving Proteins into Membranes and Organelles, Part 1

Exam Details

  • Exam #2: Thursday, October 2nd, 5:00 to 6:20 pm, Lloyd Hall, Rm 16.

Lecture Overview

  • Topic: Moving Proteins into Membranes and Organelles, Part 1.

  • Reference: Chapter 13 (pages 576-602).

Learning Objectives

  • Understand structure/function of the Endoplasmic Reticulum (ER).

  • Differentiate translation processes for cytoplasmic vs. Endomembrane System proteins.

  • Discuss protein translation mechanisms for lumenal/membrane proteins.

  • Outline the quality control processing in the ER.

  • Explain protein folding mechanisms and unfolded protein response (UPR).

Protein Targeting and ER Membrane

  • Synthesis of proteins begins on cytosolic ribosomes with signal sequences.

  • Signal Recognition Particle (SRP) and SRP receptor enable ribosome docking on the ER membrane.

Eukaryotic Protein Sorting Pathways

  • All mRNAs from nuclear DNA are translated on cytosolic ribosomes.

  • Delivery of proteins to specific cellular locations occurs during or soon after synthesis.

  • Pathways include:

    • Nonsecretory: Proteins without targeting sequences remain in the cytosol.

    • Secretory: Proteins with ER signals are directed to the Golgi, plasma membrane, or lysosomes.

Structure of the Endoplasmic Reticulum (ER)

  • Composed of Rough ER (RER) with ribosomes and Smooth ER (SER).

  • FUNCTIONS:

    • RER: Protein synthesis.

    • SER: Lipid synthesis, detoxification, calcium storage, etc.

Translation on Bound Ribosomes

  • ER signal sequence directs ribosome to the ER membrane for cotranslational translocation.

  • SRP binds to the signal sequence, processes ribosome for ER docking.

Post-Translational Translocation

  • Some proteins enter ER post-translation; BiP and Sec63 complex facilitate this.

  • Driving force is provided by BiP and ATP hydrolysis.

Membrane Protein Insertion

  • Topogenic sequences influence ER membrane protein orientation.

  • Classifications based on orientation include:

    • Type I: N-terminus in the ER lumen.

    • Type II & III: Internal signal-anchor sequences direct orientation.

Protein Modifications, Folding, and Quality Control in the ER

  • ER enzymes add oligosaccharides, form disulfide bonds, and assist proper protein folding.

  • Misfolded proteins are degraded via the ubiquitin-proteasome pathway.

Unfolded Protein Response (UPR)

  • Triggered by accumulation of misfolded proteins; increases gene transcription for chaperones.

  • If UPR fails, it can initiate apoptosis.