lecture 28/29/30 - immunoglobulin structure Flashcards
define a “family of structures”
- set of structures with a common core structure (framework or scaffold)
- same overall 3D fold but w some variations in details (implying some sequence variation)
- as a grp - bind to a larger variety of ligands, but variation is mostly localized to certain parts of structure
although they are a family, each immunoglobulin is:
unique and very specific for a particular antigen (ligand) or a set or very similar antigens
how diverse is the fam of immunoglobulins?
- from ~3000 genes
- ~100 million possible immunoglobulin sequences
explain the structure of immunoglobulins
- composed of 2 identical heavy chains (form the Y)
- and 2 identical light chains (make extensions on the upper arms of the Y)
- 12 domains (4 in each part of the Y)
- 16 disulphide bonds (one in each domain, two holding the arms of the Y together and 2 holding the bottom 2 domains of each arm together)
explain the Ig fold structure
Beta-sandwhich: -2 stacked beta sheets -~4-5 antiparrallel strands per sheet -loops connecting 2 beta sheets -one disulphide between 2 beta sheets -inward faces of each beta sheet are mostly hydrophobic (complicated connectivity)
where are the antigen binding hypervariable loops on an Ig?
the top two domains on both sides of the Y
where is the variable region on an Ig?
the top two domains on both sides of the Y
where is the constant region on an Ig?
bottom three rows of domains of the Y (bottom two on both sides of the top portion and then bottom two rows of the tail)
where is the site of cleavage for papain on an Ig?
above the disulphide bonds holding the two sides of the Y together
what is the result of cleavage by papain?
- 2 Fab (two sides of Y)
- 1 Fc (bottom of Y)
what does cleavage by papain show?
- the accessibility of the linker region btwn Fab and Fc to proteases
- illustrates how flexible the connection btwn the Fab and Fc regions
why is flexibility important for Igs?
- allows 1 IgG to bind to 2 antigens (Ag) simultaneously without needing a precise match of the distance
- i.e. bidning sites can be close together or far apart for different antigens
explain the concept of hypervariable loops in relation to Igs
- length, seq, aa composition determines shape and physiochemical properties of Igs
- e.g. to be narrow and deep vs wide and shallow
- each Ig has evolved to fit antigens tightly and specifically (they’re very complimetary)
explain the concept of an induced fit
- hypervariable loops imply no secondary structure which implies some flexibility
- e.g. when compare the structure of IgG to HIV peptide w and w/out a peptide bound there are some small structural changes
- therefore, affinity of IgG towards its antigen can be maximized
- each Ig domain is unique w/in each type of polypeptide in the IgG
- each IgG is a heterotetramer
explain the germ line DNA for one light chain
- DNA undergoes recombination and splicing, where 1 V, 1 J and the C region
- 1200 possible combinations
- errors during recombination/splicing = 3000 combinations for light chain & 5000 for heavy chain
- combining L + H = 1.5 x10^7 combinations for error
- more maturations occur during B-cell maturation bringing that number up to 10^8
