This document describes the structure and organization of cells at the molecular level. It discusses the main components of cells, including the nucleus, cytoplasm, organelles like the endoplasmic reticulum, Golgi apparatus, lysosomes, mitochondria, and peroxisomes. It also describes how proteins are sorted and transported to different locations within cells, such as the secretory pathway and nuclear transport. Protein sorting involves signal sequences that target proteins to specific organelles, and transport mechanisms include gated transport through nuclear pores as well as vesicular and transmembrane transport.
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27 - Protein Trafficking - Nuclear Transport
This document describes the structure and organization of cells at the molecular level. It discusses the main components of cells, including the nucleus, cytoplasm, organelles like the endoplasmic reticulum, Golgi apparatus, lysosomes, mitochondria, and peroxisomes. It also describes how proteins are sorted and transported to different locations within cells, such as the secretory pathway and nuclear transport. Protein sorting involves signal sequences that target proteins to specific organelles, and transport mechanisms include gated transport through nuclear pores as well as vesicular and transmembrane transport.
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Molecules, Tissues and Organisms
Nucelus- site of DNA and RNA synthesis
Cytoplasm- cytosol+ organelles Cytosol- 50% cell volume, site of protein synthesis and many metabolic pathways Organelles in the cytoplasm Endoplasmic reiticlium – 50-60% cell membrane, start point of secretory pathway Golgi apparatus – 10% cell membrane, important for sorting and modifying proteins and lipids passing through it. Lysosomes – 1% cell volume, multiple “suicide” bags for digestion of materials Mitochondria/Chloroplasts (plants) – 25% cell volume, generate ATP Peroxisomes – 1% cell volume, multiple sites for oxidative reactions Plant vacuoles – 90% cell volume, for turgor or protein storage/ degradation Protein sorting Protein synthesis mostly beings in cytosol Proteins are needed in other organelles or secreted Must be sorted Proteins that do not reside in the cytosol need sorting signals Signals part of the protein Can be short peptides at N or C termini Can be removed after use or kept if needed again 3 dimensional domains (secondary tertiary structure) Other molecules attached to the protein (post translational modifications) Signals recognized by specific receptors Triggers transfer of client protein to the destination Every organelle uses different receptors and different sorting processes If any of these processes goes wrong, cell in trouble Gated transport eg. import into and export out of nucleus. We will look at nuclear import Transmembrane transport eg. protein import into ER and mitochondria, uses transient translocation channels in the membrane Vesicular transport eg. secretion along the organelles of the secretory pathway Nuclear Transport
Nuclear pores are very abundant
Size matters for diffusion Small molecules (5kDa or less) can rapidly diffuse between cytoplasm and nucleoplasm Proteins of 20-40000 Da diffuse more slowly Proteins greater than 40kDa cannot enter RNA/ribosomes cannot exit Unless they carry nuclear localisation or export signals 22% of human proteins are nuclear and must be imported from the cytosol Assembled ribosomes have to be exported Nuclear import Since transport is through large pores fully folded proteins and ribosomal units can be transported in and out Importin binds to the NLS and the FG repeats in the FG-nucleoporins of the fibrils and channel Transient interactions with the FG ‘stepping stones’ allow movement of the complex into the nucleus through repeated binding and dissociation steps Importin receptors then disengage from the cargo NLS is not cleaved off