Antibody Maturation

Views From Molecular Modeling Workshops

Gale Rhodes (rhodes@usm.maine.edu)
Chemistry Department
University of Southern Maine
Portland Maine

First, CONFIGURE NETSCAPE to use SwissPdbViewer for viewing PDB files.

If you are unfamiliar with PDB files, see PDB CONTENTS.

Binding of Germline Antibody to Hapten

Click this link to download a comparison of 1) germline antibody (layer: GrmAb) with 2) germline antibody/hapten complex (layer: GrmAbH).

To blink between the two structures, hold down control and press tab repeatedly.

Suggestions for further exploration:

  1. Compute hydrogen bonds in both layers. Aside from the hapten-antibody hydrogen bonds, are there differences in hydrogen bonding in the two layers?
  2. Display the full structures. Superimpose heavy chains. Color by RMS. Do the heavy chain conformations change upon hapten binding?
  3. Superimpose light chains. Color by RMS. Do the light chain conformations change upon hapten binding?
  4. How would you characterize the global changes that occur in the germline antibody when it binds to the hapten?

Binding of Mature Antibody to Hapten

Click this link to download a comparison of 1) mature antibody (layer: MatAB) with 2) mature antibody/hapten complex (layer: MatAbH).

To blink between the two structures, hold down control and press tab repeatedly.

Suggestions for further exploration:

  1. Carry out the same comparisons you did for the germline antibody. How would you characterize the global changes that occur in the germline antibody when it binds to the hapten?

Two common models of protein binding to ligands are the induced-fit model and the lock-and-key model.

  1. Which model appears best to describe the binding of hapten to germline antibody?
  2. Which model appears best to describe the binding of hapten to mature antibody?

Comparison: Germline vs Mature Antibody

Click this link to download superimposed germline and mature antibody-hapten complexes.

The mutations that occur during antibody maturation are highlighted in the mature complex.

  1. How many of the mutations involve residues in contact with the hapten?
  2. How might more distant mutations produce the differences you see between germline and mature antibodies?

For Further Study:

See Structural Insights into the Evolution of an Antibody Combining Site, , G. J. Wedemayer, P. A. Patten, L. H. Wang, P. G. Schultz, R. C. Stevens, Science 1997 June 13; 276 (5319):1665

Thanks to Ray Stevens (USM, Class of 1986)

for providing atomic coordinates prior to official release.

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