Heptad breaks in alpha-helical coiled coils: stutters and stammers.
The discontinuities found in heptad repeats of alpha-helical coiled-coil proteins have been characterized. A survey of 40 alpha-fibrous proteins reveals that only two classes of heptad breaks are prevalent: the stutter, corresponding to a deletion of three residues, and the newly identified "stammer," corresponding to a deletion of four residues. This restriction on the variety of insertions/deletions encountered gives support to a unifying structural model, where different degrees of supercoiling accommodate the observed breaks. Stutters in the hemagglutinin coiled-coil region have previously been shown to produce an underwinding of the supercoil, and we show here how, in other cases, stammers would lead to overwinding. An analysis of main-chain structure also indicates that the mannose-binding protein, as well as hemagglutinin, contains an underwound coiled-coil region. In contrast to knobs-into-holes packing, these models give rise to non-close-packed cores at the sites of the heptad phase shifts. We suggest that such non-close-packed cores may function to terminate certain coiled-coil regions, and may also account for the flexibility observed in such long alpha-fibrous molecules as myosin. The local underwinding or overwinding caused by these specific breaks in the heptad repeat has a global effect on the structure and can modify both the assembly of the protein and its interaction properties.
Rosenstiel Basic Medical Sciences Research Center, Brandeis University, Waltham, Massachusetts 02254-9110, USA.
J H
JH
Brown
C
C
Cohen
D A
DA
Parry
D011487:Protein Conformation; D011506:Proteins / Q000737:chemistry*
D011506:Proteins