De Novo Design of Proteins - Peptide and Protein Design for Biopharmaceutical Applications - page 211

In most 4-helix bundles, the a-helices pack against one another as
'ridges-into-grooves' [40]. The side chains in an a-helix can be viewed
as being arranged in helical rows at the surface of the helix, thus forming
ridges and grooves. The ridges and grooves are formed by residues whose
separation in the sequence is usually four and sometimes three. The
geometry of ridges and grooves depends not only on the helix but also
on the actual sequence, i.e. its side chains. Thus, when a-helices pack
against one another, the ridges from one helix are fitted into the groove of
another. As a result, the helices that pack are inclined by an angle (often
50 or 20) relative to one another.
In artificial protein-like structures a nonlinear topology can be
achieved with templates. The peptides can be packed either parallel or
antiparallel and with varying helix crossing angles (Figure 6.3). A 4-helix
bundle can also have a 'bisecting U' topology (Figure 6.4) [2].

N N

N C

C C

C N

C C

N C N

N

N

C

Figure 6.3 Schematic topology presentation of 4-a-helix bundles, parallel and anti-
parallel, respectively, by self-assembly of helix1-loop-helix2 sequences. Here right-
handed turn loops are depicted, but left-handed turn loops are also possible (seen
from the N-terminal helix, a left-handed bundle has the second helix in the bundle to
the left, while a right-handed bundle has the second helix in the bundle to the right)
[41]. When the 'bisecting U' topology is included, this gives rise to a total of six 4-helix
bundle topologies

Figure 6.4 Schematic topology presentation of the 'bisecting U' topology of helix1-
loop-helix2 sequences [2]