Chemical Biology 03 BLOOD Biomolecular Structure Beta Structure 10/02/09

Chemical Biology 03 BLOOD Biomolecular Structure Beta Structure Lecture 11: 10/02/09

What is an Antibody? An antibody is a protein produced by your white blood cells. Antibodies are also called Immunoglobulins Antibodies detect foreign substances in your body (i.e. poison ivy toxin, polio, herpes, diptheria toxin) Antibodies initiate an immune response by activating production of killer T cells which destroy invader Over the course of an infection, new antibodies are made that become better and better at binding foreign substance (If binding is better, what happens to the Kd? ____________________________) Once your body has mounted an immune response to a substance, it will always “remember” it so the next time you become infected, you immediately make the tight binding antibodies to rapidly destroy the foreign substance. This memory is made possible through cells that are stored in your bone marrow store(called memory cells)

Structure of an Antibody Each antibody is a tetramer (H 2 L 2 ) ___ copies heavy chain (red) (H) ___ copies of light chain (blue) (L) – The foreign substance (called _______) binds at the tips of the arms in the region between the N termini of the H and L polypeptides. – The L chain folds into two domains: V L with variable sequence and C L with constant sequence. – The H chain folds into 4 domains: one variable V H and 3 constant domains – _____________ connect the 4 chains – A sugar binds to the ___________chain

Structure of an Antibody Each antibody is a tetramer (H 2 L 2 ) Two copies heavy chain (red) (H) Two copies of light chain (blue) (L) – The foreign substance (called antigen) binds at the tips of the arms in the region between the N termini of the H and L polypeptides. – The L chain folds into two domains: V L with variable sequence and C L with constant sequence. – The H chain folds into 4 domains: one variable V H and 3 constant domains – Disulfide bonds connect the 4 chains – A sugar binds to the heavy chain

Remember that Polypeptides Fold in Two Ways: Alpha helices at left Beta strands below. One strand of beta structure is represented by a thick arrow with the head towards the C terminus

IgGs are Mostly Beta Structure

Constant Both the constant and variable domains - β strands Constant domain: Seven strands are labeled A-G (see disulfide) Variable domain Nine Strands Variable domain binds antigen through loops CDR1-CDR3 Variable

Antigen binding site at tip of each arm Looked at from the top,the combining site, with the six CDR regions, contains possibility for lots of specificity. Antigen Binds here

Blood Clots Using the Fibrinogen Fibrinogen The building block of blood clots is fibrinogen hexameric molecule α 2 β 2 γ 2 Overall structure for one molecule has two edges (C- terminal) D regions), one middle (N-terminal E region), and two middle regions ( with three α - helices When fibrinogen clots, connections are made from one hexamer to the next as shown in B, C, and D

Blood Clots Using the Fibrinogen Fibrinogen