Ricerc@Sapienza

SH2 domains are protein domains that mediate protein-protein interaction through the recognition and binding of specific sequences containing phosphorylated tyrosines. The p85 protein is the regulatory subunit of the heterodimeric enzyme PI3K, an important enzyme involved in several molecular pathways. In this work we characterize the folding kinetics of the NSH2 domain of p85. Our data clearly reveal peculiar folding kinetics, characterized by an apparent mismatch between the observed folding and unfolding kinetics.

Many proteins lack a well-defined three-dimensional structure in isolation. These proteins, typically denoted as intrinsically disordered proteins (IDPs), may display a characteristic disorder-to-order transition when binding their physiological partner(s). From an experimental perspective, it is of great importance to establish the general grounds to understand how such folding processes may be explored. Here we discuss the caveats and the pitfalls arising when applying to IDPs one of the key techniques to characterize the folding of globular proteins, the Φ value analysis.

Much of our current knowledge of
biological chemistry is founded in the
structure-function relationship, whereby
sequence determines structure that
determines function. Thus, the discovery
that a large fraction of the proteome is
intrinsically disordered, while being
functional,
has
revolutionized
our
understanding of proteins and raised new
and
interesting
questions.
Many
intrinsically disordered proteins (IDPs)
have been determined to undergo a