Lecture 18: Transmembrane proteins, Golgi, COP

Peroxisome

• type of organelle called a microbody

• found in almost all eukaryotic cells

• crystalloid core: contains enzymes needed for the reaction

• involved in some enzymatic reactions

  • e.g. catabolism of very long fatty acid chains

    • reduction of reactive oxygen species (photo)

    • biosynthesis plasmalogens

    • phospholipids for the function of brians and lungs

Zellweger syndrome

• inherited in an autosomal recessive

  • severe brain development defects

  • Hypomyelination

  • Apnea (stop breathing)

  • Abnormal renal function

  • Patient usually does not survive beyond one year

Cystic fibrosis

• caused by mutation in gene, cystic fibrosis transmembrane conductance regulator (CFTR)

• the most common mutation, ΔF508, is a deletion of three nucleotides, resulting in a loss of the amino acid phenylalanine (F) at the 508th position on the protein. This mutation accounts for two-thirds (66–70%) of CF cases worldwide

Cotranslational protein import

How transmembrane proteins are integrated into a membrane

type 1 single-pass transmembrane proteins

synthesis of integral membrane proteins

How proteins are targeted to mitochondria and chloroplast

N-terminal sequences direct proteins to their respective organelles, which are eventually directed to the right compartment/membrane

• mitochondria: OMM, IMM, intramembrane space, matric

• chloroplast: OCM, ICM, thylakoid membrane/lumen, stroma

endocytic pathways for protein sorting googoo gaagaa

after a protein is fully synthesized, folded, and targeted to the ER lumen, it either:

1. stays in the ER lumen

2. transported from ER → Golgi complex → secretory pathway

   1. fully processed proteins are exported to TGN

   2. transfer of ER vesicle → Golgi is achieved by coat proteins (helps form vesicle, helps select material vesicle carries)

ER to Golgi complex

Golgi apparatus receives proteins and lipids from the ER and to other organelles, plasma membrane, or the cell exterior; proximal → distal; Cis-Golgi Network (CGN) → medial Golgi → Trans-Golgi Network (TGN)

Structure of Golgi complex

• smooth, flattened disk-like cisternae

• ~8 cisternae/stack - several 1000s

  • cisternae are biochemically unique

• curved like shallow bowl

• shows polarity

• Membrane supported by protein skeleton (actin, spectrin)

• Scaffold linked to motor proteins that direct movement of vesicles into and out of the Golgi.

Difference between Golgi complex parts

• CGN acts as a sorting station (i.e., sorts whether proteins should
  continue on to the next Golgi station or be shipped back to the ER)

• TGN sorts protein into different types of vesicles—vesicles go to plasma membrane or other intracellular destinations (e.g. lysosomes)

biochemical diversity of Golgi complex

• Proteins are modified step-wise as they traverse the Golgi.

• Different cisternae of the Golgi contain different enzymes that modify proteins.

• The differential staining of the Golgi cisternae reflects their biochemical difference

• processing plant of the cell

• involved in synthesis of polysaccharides and specific modification of protein sna dlipids (glycosylation and proteolytic modification)

Coatomer; COPI and COPII

Coat protein complex (COP) COPI and COPII are protein complexes that assemble on the cytosolic surface of donor compartment membranes at sites where budding takes place; electron micrographs reveal COPI and COPII on vesicles

• COPI in retrograde direction (opposite directions)

• COPII in anterograde direction

Key features of lysosomes

• Digestive organelles.

• Size: 25 nm to 1 μm.

• Internal pH of 4.6 (proton pump or H + -ATPase). Contains hydrolytic enzymes: acid hydrolases.

• Lysosomal membrane is composed of glycosylated proteins that act as a protective lining next to acidic lumen

Function of lysosomes

1. Autophagy: normal assembly of unnecessary/dysfunctional cellular components

2. Degradation of internalized material

1. Autophagy

Autophagosome formation → lysosome recruitment → autolysosome → digestion and release by exocytosis

• decomposition of intracellular components via lysosomes

• plays an important role in maintaining/regulating homeostasis by degrading components and providing degraded products

1. Isolation membrane derived from ER engulf target organelles to form an autophagosome (also known as autophagic vesicle)

2. Lysosome fuses with ER-derived autophagic vesicle to form an autolysosome.

3. Content of autolysosome is enzymatically digested and released (exocytosis)

2. Degradation

1. Recycling of plasma membrane components like receptors and extracellular material

2. Destroy pathogens like bacteria and viruses—only in phagocytic cells