Integral Membrane Proteins

  1. What are the integral membrane proteins?
    • selectin
    • Ig-SF
    • some integrins
    • cadherins
  2. Function of 
    • recognize and bind to a particular arrangemnet of sugars in the oligosaccharides that project from the surface of other cells
    • mediate transient interactions between circulating leukocytes and vessel walls at sites of inflammation
    • good at capturing leukocytes because they form bonds with ligands that strengthen when under mechanical stress
  3. Function of 
    • immune function, but some mediate calcium-independent cell-cell adhesion
    • cell-cell adhesion mediators first, effector role developed second
    • mediate specific interactions between both immune and non-immune cells
  4. Function of 
    • mediate Calcium-dependent cell-cell adhesion and transmit signals from the ECM to the cytoplasm
    • join cells of similar type to one another by binding to the same cadherin of a neighboring cell (homophilic binding)
    • cadherins from same cell-surface associate laterally--> parallel dimers
    • adhesion results from interaction between extracellular domains of cadherins from opposing cells to form a cell-adhesion zipper; the higher the number of interacting cadherins, the greater the strength
  5. Function of 
    • attach cells to the ECM
    • key role in integration
    • bind ligands outside and interact with proteins inside
    • cell-substratum adhesion
    • transmission of signals (inside-out and outside-in)
  6. Structure of
    • small cytoplasmic domain
    • a single membrane spanning domain
    • large EC segment that consists of a number of separate modules
  7. Structure of
    • modular construction composed of individual domains
    • extracellular part is folded into five Ig-like domains connected by disulfide bridges
    • there may be one or two other domains called fibronectin type III
  8. Structure of
    • modular construction
    • small cytoplasmic portion associated with the catenin family
    • singlepass membrane spanning segment
    • large extracellular segment consisting of five domains of similar size and structure, held by calcium
    • alpha and beta chains are both glycosylated
  9. Structure of integrins
    • two membrane spanning polypeptide chains, alpha and beta, that are non-covalently linked
    • - globular extracellular head connected to the membrane by a pair of long legs, which extend through the bilayer as a single transmembrane helix and end in a small cytoplasmic domain
    • RGD tripeptide
    • alpha chain is actually two connected by disulfide bridges and contains four divalent-cation- binding domains
    • the beta chain contains a repeating cysteine-rich region, where intrachain disulfide bonding occurs
  10. Kinds of
    • E, P, and L
    • all recognize a particular goruping of sugars that is found at the ends of the carbohydrate chains of certain complex glycoproteins
  11. Kinds of
    • VCAM
    • NCAM
    • L1
    • all mediate adhesion between non-immune cells
    • if L1 is bad--> hydrocephalus 
    • L1-deficiency disease= death
  12. Kinds of
    • E, N, P
    • called classical
  13. Calcium role in:
    used for binding of selectins to their ligands; binding of selectins to their ligands requires calcium
  14. Calcium role in:
    • no role; 
    • Ig-SFs are calcium independent
  15. Calcium role in:
    • needed; calcium-dependent cell-cell adhesion; forms bridges between successive domains of a given molecule
    • calcium maintains the EC portion in a rigid conformation that is required for cell-cell adhesion
  16. Importance of cadherins in embryos?
    • single most important factor in molding cells into cohesive tissuees in embryo and holding them together in adults
    • mediates dynamic changes requried in morphogenesis, such as epithelial-mesenchymal transition
  17. What do the cells in an embryo do?
    break away from a cohesive epithelial layer at the dorsal surface of the early embryo and wander inside as mesenchymal cells, which become mesodermal tissues
  18. What happens to E-cadherins in embryp?
    they are on the surface of the epiblast, but stop being expressed. Instead, N-cadherin begins to be expressed, forming the nervous system. N-cadherin expressed cells roll into the neural tube, eventually forming the brain
  19. What does selectin do in inflammation?
    • it will cause adhesion of leukocytes to the endothelial cells
    • When neutrophils encounter them, they form transient adhesions that slow their movement down, causing rolling.
  20. What happens after rolling of leukocytes?
    Rolling creates more interactions between other molecules on the surface, such as platelet activating factor and IgSF molecules, especially ICAM and VCAM
  21. Explain role of PAF.
    binds ot a receptor on the surface of the neutrophil, sending a signal into the neutrophil that leads to an increase in the binding activity of certain integrins already situated on the neutrophil surface
  22. IgSF molecule role?
    Binding of these causes the neutrophils to stop their rolling and adhere to the wall of the vessel, causing the neutrophils to change shape and squeeze between adjacent endothelial cells into the damaged tissues

Card Set
Integral Membrane Proteins