BIOL 435 Ch. 3 Part One (Recognition and Response) Flashcards
receptor-ligand binding
- occurs via multiple covalent bonds
- may be multivalent
- induces molecular change in the receptor
multiple noncovalent bonds
- weak individual bonds add up to strong binding affinity
- many weak bonds=great cumulative bond strength
types of non covalent bonds
- hydrogen bond
- ionic bond
- vander waals
dissociation constant (Kd)
-a measure of strength of ligand binding
-lower=stonger
>lower [ ] 1/2 lignad is bound
multivalency
-increases avidity of the interactions
affinity
-the strength of an invidivual bond
avidity
- the combined strength of multiple bonds
* an interacton may have weak affinity but high overall avidity
molecular change in the receptor
- conformational
- dimerization/clustering
- localization in the membrane
- covalent modifications
receptor interactions
-induce cascades of intracellular events
>activation of enzymes
>changes in intracellular location of molecules
lipid raft
-PM where there is a higher proportion of sphingolipid and cholesterol
>internal kinases and phosphatases
aggregation
-due to ligand binding enhance ligand binding Kd
cell-cell interactions rely on
-a binding affinity to maintain contact over long periods of time
extended contact
- facilitates signal transduction and exchange of cytokine signals
- cytoskeletal reorganization may occur
lignad-binding ability
-can be affected by receptor types and levels of expression
-different combos of receptors/protein chains change affinity
>a ligand binding may cause the other protein chains to be upregulated
level and natrue of cell-surface receptors
-tied to activation-state of the cell
Ex. activated lymphocytes upregulate IL-2Ralpha
>changes intermediate affintiy R to high affintiy R (produced alpha chain)
>IL-2 is also being upregulated
local concentrations of ligands
- cell-cell interactions allow directional release of ligands
- can increase to very high levels: increasing signal strength
immunoglobulin (Ig domains)
-contain parallel beta-strands organized as a pair of beta-sheets
-hydrophilic and hydrophobic AA alternate
>hydrophobic AA face centre
-stabilized by disulfide bonds
-forms ‘hydrophobic sandwich’
examples of Ig domains in molecules
- Ig molecules (antibodies)
- T-cell accesory proteins (CD)
- adhesion molecules
- MHC molecules
beta-sheets in Ig domain
-are connected by variable loops
>CDR-1, CDR-2, CDR-3
-key to variability of An binding sites
CDR
-complementary determining regions
loops
- often contain hydrohilic residues (2-16)
- found on protein surface
- connect helices and sheets
- allow protein folding
- reverse direction of peptide
hypervariable loops
-responsible for sequence and structural diversity in Ab and TCR
immune receptors
- bear Ig domains
- can be transmembrane, cytosolic or secreted
soluble/secreted Ab
-Ig lacking the carboxyl terminus transmembrane segment is secreted
BCR
- B-cell receptor
- contains an antibody of defined specificity
TCR
- T cell receptor
- speicific for peptide antigens presented by MHC molecules
- peptides derived from proteins degraded by APC
- CD4 and CD8 are T-cell coreceptors that devine different subsets of T-cell function
3 hypervariable regions
-of AA are found in variable heavy and variable light regions
-complementaryity-determining regions
>CDR3 is most variable
-heavy chain is most variable
*come together to form the antibody combining site
framework region
- invariant AA interspersed near each CDR
- responsible for the folding of the CDRs to form the Ab combining site
quaternary protein
- is made up of 2 identical heavy chains and 2 identical light chains
- hinge region
- 1 or 2 disulphide bonds
- 2 or 3 Ig domains in effector region of heavy chains
hinge region
-can help the Ab bind in 2 places
An specificity
-determined by structure of variable regions at ends of light/heavy chains
Ab effector activity
- eg. phagocytosis and complement fixation
- a function of the interaction of the constant regions of the heavy chain
