Protein ligand interactions Flashcards
specific recgonition of foreign molecules
specific and tight binding of proteins in the immune system to foreign organisms
sites on foreign molecules are called antigenic determinants and interact with antigen receptors
humoral
antibodies
B cells with immunoglobulins on surface
antigen activated b cells with antibody on surface that can bind antigen
triggers production of a clone of identical B cells that secrete soluble antigen-binding immunoglobulins into the bloodstream
foreign recognition by t cell receptors
recognise virus infected cells
TCR binds degraded fragments of the antigen when they are associated with an MHC molecules
antibodies contain multiple domains
the immunoglobulin IgG molecule is made up of 2 copies of 2 polypeptide chains
heavy and light
disulphide bridges line up the 4 chains
the l chain fold into 2 domains Vl with variable sequence between different IgG molecules and Cl with constant sequence
the H chain fold into 4 domains: one variable Vh and 3 constant domains Ch1 and Ch2 and Ch3
2 identical antigen binding sites are at the ends of the variable domains - antigen binding sites
electron microscopy shows
antibodies have inter domain flexibility in solution
can be crystallised = symmetric homodimers by have aysmmetric structure
antibodies can adapt to a greater variety of positions
complementarity determining regions
variable domains are not uniformly variable throughout their length
hyper variable regions - higher variability than the rest
CDRs vary both in size and sequence among different immunoglobulins
CDRs determine the specificity of antibody-antigen interaction
50 million AB producing B cells each produces an Ab that is unique to that cell and its progeny
genetic info for this diversity is contained in less than 1000 small DNA segments
variable domains are made by combinatorial joining of the gene segments resulting in 90k diff H chains and 3k diff L chains
the number of diff Ab molecules is 90k*3k =270 million
immunoglobin Ig fold
all constant domains are folded into a antiparallel Beta sandwich mae of one 3 stranded beta sheet pracked against a 4 stranded beta sheet
topology is a greek key barrel
the fold is the same in both heavy and light chains
the loops between the strands are short so most residues are in the beta sheets
most invariant residues occur in the beta sheets where they are involved either in the hydrophobic core of the domain or in interactions between constant domains to form the structure of the complete IgS molecule
in heavy and light held together in
probably evolved from common ancestral protein
2 classes of MHC
1 - on surface ofmost cells protection fromviral infection
expressed by all cells
2 polypeptide chains
heavy - cpans membrane bilayer
extracellular region 3 domains a1 2 3
a1 and 2 each made up 4 antiparallel beta sheets with a helix sitting across the top
= the 2 domains associate
together by anti parallel beta sheet joined by hydrogen bonding - continuous 8 layer beta sheet
beta sheet floor sits ontop of and is established by a3
2 helices almost parallel lining sides of a wide crevice that forms the antigen binding site
light - non covalently attached microglobin
2 - found on specialised APC that pick up proteins and stimulate the immune system when they ffind a foreign peptide - dendritic cells of the lymph node
peptide binding by class 1 mhc moelcles
peptides bind by thei r N and C termini buried in the peptide binding site and their central regions exposed + bulge out eom the cleft
sets of residues conserved in class 1 mhc prteins form hydrogen bonds with these buried termini
peptide side chains are bound to small pockets within the cleft - important for overall peptide binding affinity
residues with side chains that point away from MHC do not contribute to the binding but are presented to the t cell receptor
how can a few different MHC molecules recognize and bind an almost unlimited no of antigens when each cell can only build a few different mhc protein molecules
degeneracy in the antigen recognition
mhc grips the antigen polypeptides at each end and in the middle
T cells see antigen and MHC molecules which are firmly t the surface of APCs as one single structure
mhc peptide complexes are recognised as single surface by t cell receptors
with the hyper variable loops burying the antigenic peptide
binding is stabilised by and interaction between the MHC and complementarity determining CD proteins on the T cel surface
the proteins are membrane anchored by hinges allowing considerable flexibility
recognition of antigen in MHC vs immunoglobulins
antibodies recognise and are sensitive to confirmation of the antigen
big binding sites
MHC proteins recognise peptide antigens based on their sequence and force the antigeninto an extended conformation = displaying it to the T cell receptor
the shape and location of charged non polar and hydrogen bonding groups in the protein and ligand are complementary
TCR structure
heterodimeric transmembrane glycoproteins in only t cells
each TCR chain forms half of an extracelular antigen binding domain
TCRs have variable and constant immunoglobulin domains and hypervaribale regions that provide binding specificity
binding specificity between proteins in the immune system is conferred by clinical complementarity between the antigen and its specific binding site on the antibody or the T cell receptor.
The shape and location of charge to non polar hydrogen bonding groups are complementary e.g. binding site w a negatively charged group may bind an antigen with a positive charge in the complementary position
Antibodies recognise a wide variety of different molecular species and confirmations and are sensitive to the confirmation of the antigen.
MHC recognise peptide antigens based on their sequence. Force the antigen into an extended confirmation that displays many of the side change to the T cell receptor
Unlike antibodies, t cell receptors recognise antigen only when it his brain in the peptide binding site of an MHC. protein
