Antibody loops

In conclusion, this work confirms that with the current PDB, modeling antibody CDRs is better achieved by using a database of CDRs from antibody molecules rather than other molecules. Nevertheless, calculation of the conformational free energy is essential in order to select the best CDR conformation for a current model. Although we have currently applied the present method to antibody loops, it appears to be a promising approach for screening an ensemble of loop conformations for any protein structure framework. ... 

RM Fine, H Wang, PS Shenkm, DL Yarmush, C Levmthal. Predicting antibody hypervariable loop conformations. II Minimization and molecular dynamics studies of MCP603 from many randomly generated loop conformations. Proteins 1 342-362, 1986. 

ACR Martin, JC Cheetham, AR Rees. Modeling antibody hypervariable loops A combined algorithm. Proc Natl Acad Sci USA 86 9268-9272, 1989. 

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... 

The shape of the interaction area between lysozyme and the CDR loops of the antibody is easily distinguished from the hapten-binding crevice. The interaction extends over a large area with maximum dimensions of about 20 X 30 A (Figure 15.15). The interaction surface is irregular but relatively flat, with small protuberances and depressions that are complementary in the antigen and the antibody. Residues from all six CDR loops contribute to the... 

Figure 15.22 T-cell receptor stucture shown as a ribbon diagram. The anbgen-binding site is formed by CDR loops (labeled 1 to 3) from the Va and Vp domain, as for antibodies.

Bruccoleri, R.E., Haber, E., Novotny, J. 5tructure of antibody hypervariable loops reproduced by a conformational search algorithm. Nature 335 564-568, 1988. 

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. 

The small luminal loop in the proposed structure of Ca -ATPase [11] between transmembrane helices 7 and 8 (residues 870-890) was suggested to contain the epitope for mAb A20 [139], and for an antipeptide antibody directed against the 877-888 sequence (TEDHPHFEGLDC) of the Ca -ATPase [138],... 

Essentially identical conclusions arose from the studies of Matthews et al. [138], An anti-peptide antibody directed against the cytoplasmically exposed C-terminal region of the Ca " -ATPase (985-994) reacted freely in native sarcoplasmic reticulum, in agreement with earlier observations [137], while the antibody directed against the putative luminal loop (877-888) reacted strongly only after solubilization of sarcoplasmic reticulum with Ci2Eg, Purified ATPase preparations reacted freely with both antibodies under both conditions. A 30-kDa protease-resistant fragment obtained... 

FIG. 4.1. Schematic representation of two antibodies reacting with a continuous and a discontinuous epitope of a protein antigen interacting residues are indicated in black. If the individual loops of a discontinuous epitope are able to bind to the antibody paratope on their own, they may be given the status of continuous epitope. The inset shows the three loops of an antibody VH chain which form part of the paratope... 

Human immunodeficiency virus (HIV) type 1 gpl20 (V3 loop) protein Alfalfa mosaic virus in tobacco leaf Elicited specific virus-neutralizing antibodies in mice when delivered parenterally. 16... 

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