16.1 Protein targeting to organelles

Proteins need to find their way around the cell, and signal sequences are their GPS. These short amino acid tags guide proteins to specific destinations like the ER, mitochondria, or nucleus. It's a crucial process for cellular organization and function.

Getting proteins where they need to go involves specialized transport systems. Translocons act as cellular gateways, allowing proteins to cross membranes. This can happen as proteins are being made or after they're fully formed, depending on their final destination.

Protein Targeting and Translocation

Role of signal sequences

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• Short amino acid sequences direct proteins to appropriate cellular destinations
  • Located at N-terminus of polypeptide chain
  • Recognized by specific receptors on target organelle (ER, mitochondria, nucleus)
• Different types of signal sequences target proteins to various organelles
  • ER signal sequence directs proteins to endoplasmic reticulum
  • Mitochondrial targeting sequence guides proteins to mitochondria
  • Nuclear localization signal facilitates protein import into nucleus
• Signal sequences cleaved off by signal peptidases once protein reaches destination

Mechanisms of protein translocation

• Protein translocation occurs through specialized protein complexes called translocons
  • Translocons form channels in membrane to allow protein passage
• Translocation can be co-translational or post-translational
  • Co-translational translocation involves simultaneous synthesis and translocation of proteins (occurs in ER)
  • Post-translational translocation involves translocation of fully synthesized proteins (occurs in mitochondria, chloroplasts, peroxisomes)
• Energy for translocation provided by ATP hydrolysis and proton gradient across membrane

Co-translational vs post-translational targeting

• Co-translational protein targeting
  • Protein synthesis and translocation occur simultaneously
  • Involves signal recognition particle (SRP) and SRP receptor
  • Mainly associated with proteins destined for ER
• Post-translational protein targeting
  • Protein fully synthesized in cytosol before translocation
  • Requires chaperone proteins to maintain unfolded state of protein
  • Associated with proteins targeted to mitochondria, chloroplasts, peroxisomes
• Timing of translocation relative to protein synthesis main difference between two mechanisms

Function of signal recognition particle

• SRP is ribonucleoprotein complex that facilitates co-translational protein targeting
  • Composed of small RNA molecule and six protein subunits
• SRP recognizes and binds to ER signal sequence of nascent polypeptide chain
  • Binding occurs as signal sequence emerges from ribosome
• SRP-ribosome complex then binds to SRP receptor on ER membrane
  • Interaction between SRP and receptor causes pause in protein synthesis
• Ribosome transferred to translocon and SRP released
  • Protein synthesis resumes and polypeptide chain co-translationally translocated into ER lumen
• SRP ensures efficient targeting of proteins to ER and prevents premature folding of polypeptide chain