Antibodies are proteins too!

Date:

The third complementarity-determining region loop on the IgG heavy chain (CDR H3) is the focal point of the gene recombination that gives rise to the immense diversity of antibodies. A consequence of this diversity is observed in the variability in length, sequence and structure of the H3 loop. Because of the circumstances that give rise to the H3 loop, it is unclear if the conformations they adopt are unique to antibodies. We set out to determine what it means for a loop to have an H3-like conformation and whether or not these conformations are commonplace in other proteins. To that end, we searched a set of high-quality non-antibody structures for regions with 1) 3D transformations matching the conserved transformation of the H3 loop and 2) a C-terminal “kink”/“bulge”. We found these criteria were enough to identify a set of loops with similar DSSP code distributions and RMSDs within 2.0 Å of nearly all H3 loops of length 15 or shorter. We believe this set can be used to find starting structures for H3 loop modeling and that this result is powerful evidence suggesting that CDR H3 is just another loop.