Antibodies regions

Boulianne, G.L., Hozumi, N., Schulman, M.J. (1984). Production of functional chimaeric mouse/human antibody region domains. Nature, 312, 643-646. 

Antibodies region or the highly variable regions from the Vg and Vg regions. These... 

Percus J K, Percus O E and Perelson A S 1993 Predicting the size of the T-cell receptor and antibody combining region from consideration of efficient self-nonself discrimination Proc. Natl Acad. Sci. USA 90 1691-5... 

S-Fl Jung, I Pastan, B Lee. Design of interchain disulfide bonds m the framework region of the Fv fragment of the monoclonal antibody B3. Pi otems 19 35-47, 1994. 

The residues not in the framework region form the loops between the p strands. These loops may vary in length and sequence among immunoglobulin chains of different classes but are constant within each class the sequence of the loops is invariant. The functions of these loops are not known, but they are probably involved in the effector functions of antibodies. When an antibody-antigen complex has been formed, signals are... 

IgG antibody molecules are composed of two light chains and two heavy chains joined together by disulfide bonds. Each light chain has one variable domain and one constant domain, while each heavy chain has one variable and three constant domains. All of the domains have a similar three-dimensional structure known as the immunoglobulin fold. The Fc stem of the molecule is formed by constant domains from each of the heavy chains, while two Fab arms are formed by constant and variable domains from both heavy and light chains. The hinge region between the stem and the arms is flexible and allows the arms to move relative to each other and to the stem. 

Figure 17.2 An example of prediction of the conformations of three CDR regions of a monoclonal antibody (top row) compared with the unrefined x-ray structure (bottom row). LI and L2 are CDR regions of the light chain, and HI is from the heavy chain. The amino acid sequences of the loop regions were modeled by comparison with the sequences of loop regions selected from a database of known antibody structures. The three-dimensional structure of two of the loop regions, LI and L2, were in good agreement with the preliminary x-ray structure, whereas HI was not. However, during later refinement of the x-ray structure errors were found in the conformations of HI, and in the refined x-ray structure this loop was found to agree with the predicted conformations. In fact, all six loop conformations were correctly predicted in this case. (From C. Chothia et al.. Science 233 755-758, 1986.)...

Homologous proteins have similar three-dimensional structures. They contain a core region, a scaffold of secondary structure elements, where the folds of the polypeptide chains are very similar. Loop regions that connect the building blocks of the scaffolds can vary considerably both in length and in structure. From a database of known immunoglobulin structures it has, nevertheless, been possible to predict successfully the conformation of hyper-variable loop regions of antibodies of known amino acid sequence. 

Biologicals. Figure 3 Fusion protein construction combination of the molecular component of interest with the constant region (Fc) of an antibody molecule, usually immunoglobulin (lg)G1 Fc, imparts the Fc function on to the molecularcomponentfortherapeutic use. The example given is ofCTLA4-lg, derivatives of which have shown clinical efficacy in the treatment of rheumatoid arthritis and transplant rejection. 

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