Protein Structure Flashcards
Protein Structure
amino acids and polypeptide chain
Polypeptide chain
peptide bond and phi, psi conformation
Monoclonal
-produced from single B-lymphocyte clone and bind same epitope
monoclonal antibodies (mAbs)
-used in research and therapy
-treat cancer, inflammatory disease, infectious and cardiovascular disease
-rapidly growing in use
OKT3
-first therapeutic mAb approved
-targets CD3 on T cells
-depletes T cells
-immunosuppressor in preventing transplant rejection
IgG antibody chains
-heavy and light (2 of each)
-constant or variable
Light chain
VL CL
Heavy chain
Vh3Ch
Ig domains
-Ig fold packed with hydrophobic residues (keep folded and stable)
-110-amino acids
-sandwich of 2 antiparallel sheets linked by disulfide bonds
Ig Fragments
-2 Fab regions
-Fc region
Fc region
-stem of Ig
-binds Fc receptors
-activates complement-mediated cytotoxicity
Full IgG antibody
-2 light chains with one VL and one CL
-2 heavy chains with one Vh and 3 CH’s
-2 copies of 2 chains
-Ig fold domain
-saccharide component
Where does the hydrolysis producing Fab and Fc occur?
Hinge peptide (in the middle)
saccharide component
in the constant H domains
IgG flexibility
-due to loops between Ig domains
-Fab and Fc orientation varies among Ig molecules
Protein function
dependent on binding and recognition
molecular recognition
-highly specific
-complementarity
-noncovalent interactions
Induced-fit
-structural changes occuring to enhance specificty and complementarity
Variable domains
-comprised of 3 hypervariable loops
Hypervariable loops
-comprised by variable domains
-vary in length and sequence in IgGs
-H and L chains (pic) (fab region)
-exact match between antigen and loops
Loop matching antigen
-high affinity
-induced fit
-specificity
Therapeutic Antibody mechanisms
-targeting extracellular ligand-receptor interactions
-antigen binding affinity is key
Ligand-receptor interactions
-bind to ligand or receptor (blockade)
-can lead to receptor down regulation
Human IgA monoclonal antibody
-blocks SARS-CoV-2 spike protein interaction with human ACE2 receptor
-forms MAb363 SARS-CoV-2 RBD complex
Monoclonal IgG molecules effectively recognize one antigen with high affinity because
the sequences of the hypervariable loops are selected to exquisitely complement the 3D shape of the
antigen.
Antigens are recognized with high affinity by antibodies because
the sequences of three hypervariable loops are selected in an immune response to exquisitely complement the 3D shape of the antigen.
The assigned reading “Therapeutic monoclonal antibodies,” describes several types of engineered antibody molecules that have been developed for therapeutics. Which of the names below does NOT refer to a type of therapeutic monoclonal antibody?
Fab
Fc
BiTE®
scFv
Fc
Twelve domains compose an IgG molecule. Of these domains,
all have two or more cysteine residues.
Disulfide Bridge
bond between light and heavy chains of Fab
Protease
-cleaves backbone
-pepsin
pepsin
-protease
-cleaves hinge peptide
=2 Fab + Fc
How many IgG domains
-12 domains
-4 variable (1 light, 1 heavy) x2
-8 constant (3 heavy, 1 light)x2
Acidic Residues
aspartic (R), glutamic (E)
Basic residues
lyseine and arginine
receptor blockade
-antibody binds to receptor
-ligand cannot bind to receptor
-could lead to endocytosis and removal of cell
