Ricerc@Sapienza

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
disorder to order transition when
recognizing their physiological partners,
suggesting their mechanisms of folding are
intrinsically different from those observed
in globular proteins. However, IDPs also
follow some of the classic paradigms
established for globular proteins, pointing
to important similarities in their behavior.
In this review, we compare and contrast the
folding mechanisms of globular proteins
with the emerging features of binding-
induced folding of intrinsically disordered
order transitions of intrinsically disordered
proteins appear to follow rules of globular
protein folding such as the cooperative
nature of the reaction, their folding
pathways are remarkably more malleable,
due to the heterogeneous nature of their
folding nuclei, as probed by analysis of
linear free energy relationship plots. These
insights have led to a new model for the
disorder-to-order transition in IDPs termed
‘templated folding’, whereby the binding
partner dictates distinct structural
transitions en route to product, while
ensuring a co-operative folding.