Chemical Biology 03 BLOOD

1. Chemical Biology 03BLOOD Biomolecular Structure Beta Structure 10/02/09 www.optics.rochester.edu/.../image007.gif

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

3. 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)

4. Structure of an Antibody • Each antibody is a tetramer (H2L2) • ___ 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: VL with variable sequence and CL with constant sequence. • The H chain folds into 4 domains: one variable VH and 3 constant domains • _____________ connect the 4 chains • A sugar binds to the ___________chain

5. Structure of an Antibody • Each antibody is a tetramer (H2L2) • Twocopies 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: VL with variable sequence and CL with constant sequence. • The H chain folds into 4 domains: one variable VH and 3 constant domains • Disulfide bonds connect the 4 chains • A sugar binds to the heavy chain

6. 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

7. IgGs are Mostly Beta Structure

8. IgGs are Mostly Beta Structure

9. Variable 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

10. 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

11. Blood Clots Using the Fibrinogen • The building block of blood clots is fibrinogen • hexameric molecule • α2β2γ2 • 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 Fibrinogen

12. Blood Clots Using the Fibrinogen Fibrinogen