Chemistry Reference
In-Depth Information
coil structure, the a and d positions should be occupied by hydrophobic amino acids
to form the interior hydrophobic seam whereas the e and g positions are populated by
charged amino acids to render additional stability through electrostatic interactions.
The selection of amino acids at each position controls the oligmerization state and
the relative orientation of each helix within a coiled coil, such as dimer versus
trimer, tetramer, and higher ordered assembly up to seven helices, or parallel
versus antiparallel arrangement. The axial elongation of coiled coil proteins and
the side-by-side packing against one another leads to the formation of many types
of functional proteins and protein matrices. For example, tropomyosin, in the form
of a dimeric coiled coil, regulates the interaction between F-actin filaments and
myosin in response to Ca
2
þ
. Parallel coiled coil trimers adopted by the HIV virus
coat help the entry of HIV into human cells through the fusion of the hydrophobic
N-termini with the cell membrane. As a major component of the cytoskeleton, inter-
mediate filaments composed of coiled coil tetramers play an important role in provid-
ing mechanical strength to the nucleus and other cellular components. Understanding
the rules of self-assembly utilized by Nature has been and will continue to be a major
challenge for researchers.
A number of research groups have taken up this challenge and have developed
rationally designed peptides adopting coiled coil structures that self-assemble into
more complex nanostructures. As a dominating and perhaps the most practical
form of nanostructures, nanofiber assembly serves to illustrate the hierarchical mol-
ecular self-assembly possible in these systems.
The first report on the formation of a-helix based nanofibers by Kojima and
coworkers (1997) described a peptide comprising three heptad repeats that self-
assembled into a coiled coil tetramer at near neutral pH in the presence of salts.
Analytical ultracentrifugation indicated that not only was atetramer formed but also
a species with a high molecular weight, which later was identified by negatively
stained transmission electron microscopy (TEM) as nanofibers with 5-10 nm
diameters. The same group explored the stability of helices and the resultant nanofi-
bers through sequence reversal design and showed that unexpected enhanced helix
stability and fiber elongation was observed with peptides with a primary sequence
reversed from the originally designed peptide (Kojima et al. 2005). Hypothetically,
the unequal charge distribution after sequence reversal may cause the self-assembly
into more stabilized higher ordered aggregation by the formation of salt bridges.
Although a more detailed description of the fiber formation and elongation needs
to be discussed in terms of the hierarchical design, the work took the initial step
toward the development of a-helix based artificial nanofibers.
Following this early study, Woolfson's group designed a series of peptides that
have the ability to self-assemble into a dimeric coiled coil utilizing a “sticky-end”
assembly mechanism (Pandya et al. 2000). The idea of the rational design of such
a structure was motivated by the staggered pattern of subunits leading to the for-
mation of natural fibrous structures, such as intermediate filaments, and the principle
utilized by self-assembled DNA systems to create a variety of nanostructures.
The molecular design shown in Figure 14.1 involves two four-heptad a-helices
(SAF-p1 and SAF-p2) that prefer to form a coiled coil dimer with an overhanging
