Post 15: A single amino acid can make a difference 🧐

The folding of a protein depends on the energy and geometry provided by each of its residues and the environment in which it is found. In turn, foldings give more or less freedom of movement, allowing certain functions such as catalysis in enzymes.

A very curious case in this regard is proteins with interchangeable foldings (AKA switching proteins), which, due to a single amino acid (in the correct position), can completely change their folding. For example, proteins GA98 and GB98 differ only in a single amino acid at position 45 in the sequence (highlighted in cyan in the cartoon prediction made with AlphaFold2). GA98 with a Leucine adopts an alpha-helix conformation, while GB98 with a Tyrosine adopts a configuration with alpha and beta sheets folded. This property is also captured by AlphaFold2 by correctly predicting these different foldings generated by a single different amino acid.

Refs:

1. One sequence plus one mutation equals two folds