A Special Fold?

A protein is a chain of amino acids that folds into a particular three dimensional conformation.  A fold is a particular conformation.  What science has discovered is that even though amino acid sequence variability is immense (for a protein of 100 amino acids there are 20^100 possible combinations, since there are 20 different amino acids), there are only  about 1000 or so shapes/folds that are employed by life.

You can think of a fold as a region where the amino acid chain is arranged into a scaffold.  Function is tied to the scaffold when it is decorated with an active site (which is usually some cleft or groove on the protein’s surface that binds a substrate and converts it to a product), and/or with other binding sites.

The immunoglobulin fold is a particular scaffold arrangement that is used to make antibodies (this scaffold is also found in many other proteins).

So I would like to pose a question that, as far as I have been able to determine, has never been asked.

While it is clear that mutations and selection play key roles in the generation of antibodies, is it possible that the immunoglobulin fold itself facilitates this somatic “evolution?” In other words, is there something special about the immunoglobulin fold such that mutations and selection would not be nearly as successful in generating antibody-function if another fold was used?
I ask this because the immunoglobulin fold, which is universal among all domains of life, seems especially robust when it comes to tolerating mutation, yet retaining the same basic 3D shape.  There are proteins with immunoglobulin folds that possess 5% sequence identity and have different functions.  In fact, so widespread is this fold that one study that attempted to evaluate protein folds among the three domains had to exclude this fold “because of the over-representation of immunoglobulin-like sequences in the NR database that made the analysis of this fold very computationally intensive.” And to this day, people are still trying to figure out whether the various immunoglobulin folds are related by descent or keep popping into existence by convergent evolution.

Consider the possibility that not all protein folds are equally “evolvable” and that the immunoglobulin fold is rather exceptional in its evolvability.  Could adaptive immunity, successful as it currently is, exist without this fold?

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