ROP Cross Section
ROP Cross Stereo
4-Alpha Helix Bundle Proteins
The protein structures examined in the original description of the 4-alpha helical bundle motif in 1980 manifest little apparent sequence homology and were generally constructed of relatively short alpha helices. Nevertheless, it was clear that the most compact arrangement of 4 alpha helices with similar lengths and short interconnections was an antiparallel bundle. The most symmetric arrangements had an “hourglass” shape with points of closest inter-helical approach at the centers of each helix. However, most observed structures had a point of closest interhelical approach at one end of the bundle, making them wedge-shaped.
4-Alpha Helical Bundle Superstructures
4-Alpha Helix Bundle Interhelical Contacts
Alpha Helix Net (after Crick 1953)
Alpha Helix Interactions at ~20 Degrees
4 Alpha Helix Bundle Geometry & Packing Symmetry
Stereo Views of Model 4 Helix Bundle Packing at 18 Degrees
Dyad Related 4 Helix Bundle Packing
4(1) Screw 4-Helix bundle Packing
The cytochrome b562 from E. coli was observed to be a 4-alpha helical bundle protein with architecture similar to monomer of the cytochrome c-prime derived from the photosynthetic bacterium Rhodopseudomas molischianum. This was a bit surprising since the protoporphyrin IX heme group in cytochrome c-prime is covalently connected to the polypeptide backbone through thioether linkages to protein cysteine groups (a defining property of c-type cytochromes), whereas the heme was non-covalently bound in cytochrome b 562. Nevertheless, a least square superposition of the heme groups in the two structures showed a surprising correspondence between the both the alpha helical frameworks of the two structures as well as the situation of several aromatic amino acid side chains surrounding the heme groups. Is this a manifestation of convergent or divergent evolution?
Cytochrome b562 and Cytochrome c-Prime
Alpha Helix Macro Dipoles
The contiguous H-bond networks that stabilize the alpha helical conformation create a helical macrodipole.
In a collaborative study with Bob Sheridan and Ron Levy, interaction of the helix macrodipoles were determined to be an energetically favorable contributor to the antiparallel helix arrangements found both in 4-alpha helical bundle proteins and their aggregated superstructures.
H-Bond Networks in Cytochrome c-Prime Dimer
Dipolar Stabilization in 4-Alpha Helical Superstructures