9. Protein folding, chaperones, prions. Posttranslational modification of proteins. Senescence and degradation of proteins.
Covers how cells sort proteins to their compartments, including nuclear, mitochondrial, and secretory routes, and what happens when lysosomal sorting fails. It then explains protein folding, the role of chaperones, and prion misfolding with spongiform encephalopathies. Finally it outlines post-translational modifications such as limited proteolysis, glycosylation and phosphorylation, ending with ubiquitin-tagged protein degradation.
Inside: 1 section · 1 labelled picture · 4 min
Topic 9 of 64 in the MU Sofia syllabus for Biology (Dental Medicine, Year 1). The free AceMed note covers it in 1 section, about 542 words (4 min of reading).
In this note
Introduction
Introduction
Protein Sorting
Directs proteins to specific cellular compartments.
3 Ways of Protein Transport:
Gated Transport:
For nuclear proteins, passing through nuclear pore complex.
Transmembrane Transport:
Proteins pushed through lipid bilayer.
Vesicular Transport:
Proteins enclosed in vesicles, traveling and fusing with organelles.
Sorting of Nuclear Proteins:
Nuclear pores allow gated transport of large molecules.
Proteins with nuclear localization signals recognized and transported.
Nuclear Localization Signals:
Short peptide sequences retained in the nucleus.
Mutations in these signals lead to cytoplasmic retention.
Sorting of Mitochondrial Proteins:
Long signal peptides direct proteins to mitochondria.
Protease removes signal peptide after translocation.
Sorting of Surface, Secreted, and Lysosome Proteins:
Trafficked between endomembranes via export pathway.
Export Pathway:
Proteins synthesized on rER translocated to ER lumen.
Vesicular transport to Golgi complex and destination (cell surface or lysosomes).
Three Ways out of Golgi:
Constitutive secretion, regulated secretion, and pathway to lysosomes.
When Sorting of Lysosomes Fails:
Mannose-6-phosphate deficiency leads to exocytosis instead of lysosomal targeting.
Retrograde Trafficking from Endosome to Trans-Golgi Network:
Endosomes sort cargo for lysosomal degradation or retrograde transport.
3 Ways out of Golgi:
Constitutive Secretion:
Default pathway for protein export.
Regulated Secretion:
Proteins packaged into secretory vesicles, exocytosed upon signal.
Vesicles coated with clathrin protein.
Pathway to Lysosomes:
COPII proteins form vesicles from ER to Golgi complex.
COPI proteins form vesicles in the reverse direction and for intra-Golgi transport.
When Lysosomal Sorting Fails:
Mutation impairs mannose-6-phosphate synthesis.
Lysosomal enzymes misdirected.
Exocytosed via constitutive secretion.
Lack of lysosomes.
Undigested materials accumulate.
Forms abnormal, harmful inclusions.
Retrograde Trafficking from Endosome to Trans-Golgi Network:
Endosomes receive cargo from endocytosis.
Cargo sorted:
Lysosomal degradation via multi-vesicular body (MVB).
