Biology Reference
In-Depth Information
while the overall fold of proteins is often well conserved even at unde-
tectable levels of sequence similarity, protein function — such as enzyme
function and specificity — shows much higher variability,
43,44
even at high
levels of sequence identity (above 50%). Functional assignment of protein
function thus requires new methods beyond simple homology-based
assignments which take into account specific local structural features.
4.2.2. Unstructured proteins
Unstructured regions in proteins are implicated in important biological
roles such as translation, transcriptional regulation, cell signaling, and
molecular recognition. Therefore, they have recently become the focus
of much attention. Several studies report examples of disordered proteins
implicated in important cellular processes, undergoing transitions to
more structured states upon binding to their target ligand, DNA, or
other proteins.
45-47
New biological functions linked to native disorder are
emerging, such as self-assembly of multi-protein complexes
48
or involve-
ment in RNA and protein chaperones.
49,50
Unstructured proteins pose a
serious challenge for experimental structural determination, as they can
hinder the crystallization of proteins or interfere with NMR spec-
troscopy. Consequently, such proteins are also not amenable to compar-
ative modeling techniques. However, computational approaches for
detecting regions in protein sequences with high propensity for intrinsic
disorder have been successfully developed based on the observation that
such protein segments share characteristic sequence properties.
51-54
Furthermore, molecular dynamics (MD)-based methods have been suc-
cessfully applied to certain proteins of this category, and are used to ana-
lyze and understand the path of folding and unfolding in self-assembling
multi-protein complexes.
48
4.2.3. Membrane proteins
Membrane proteins are involved in a broad range of central cellular
processes, including signaling and intercellular communication, vesicle
trafficking, ion transport, and protein translocation. Their particular
cellular location and central role in many disease mechanisms make them
