Intrinsically unstructured proteins and their functions.
H. Jane Dyson and Peter E. Wright
Nature Rev. Mol. Cell Biol.6:197-208.
"Disordered regions can be highly conserved ..."
and may function by binding to target structures (thereby folding),
as flexible linkers between domains, or in other ways.
Extended disordered proteins: targeting function with less scaffold.
Kannan Gunasekaran, Chung-Jung Tsai, Sandeep Kumar, David Zanuy and Ruth Nussinov
Trends Biochem. Sci. 28:81.
Argues that proteins involved in extensive protein-protein interactions
can function effectively despite having their structure depend upon
such interactions, so that as monomers they are
natively disordered. Dispensing with the
structural framework (scaffold) needed to maintain a stable fold in the
monomer increases efficiency by reducing size. This may account for the
large percentage (roughly half) of all
proteins that are predicted to be natively disordered.
The disorder of intrinsically unstructured proteins (IUP's) is
crucial to their functions. They may adopt defined but extended structures
when bound to cognate ligands. Their
amino acid compositions are less hydrophobic than those of soluble proteins.
They lack hydrophobic cores, and hence do
not become insoluble when heated. About 40% of eukaryotic proteins have at
least one long (>50 residues) disordered region. Roughly 10% of proteins in
various genomes have been predicted to be fully disordered. Presently
over 100 IUP's have been identified; none are enzymes.
Obviously, IUP's are greatly underrepresented in the Protein Data Bank, although
there are a few cases of an IUP bound to a folded (intrinsically
structured) protein. Here, Tompa
suggests five functional categories for intrinsically unstructured proteins
and domains: entropic chains (bristles to
ensure spacing, springs, flexible spacers/linkers), effectors (inhibitors
and disassemblers), scavengers, assemblers, and display sites.