title: Extended knobs-into-holes packing in classical and complex coiled-coil assemblies.
abstract: This year marks the 50th anniversary of Crick's seminal paper on the packing of alpha-helices into coiled-coil structures. The central tenet of Crick's work is the interdigitation of side chains, which directs the helix-helix interactions; so called knobs-into-holes packing. Subsequent determinations of coiled-coil-protein sequences and structures confirmed the key features of Crick's model and established it as a fundamental concept in structural biology. Recently, we developed a program, SOCKET, to recognise knobs-into-holes packing in protein structures, which we applied to the Protein Data Bank to compile a database of coiled-coil structures. In addition to classic structures, the database reveals 4-helix bundles and larger helical assemblies. Here, we describe how the more-complex structures can be understood by extending Crick's principles for classic coiled coils. In the simplest case, each helix of a 2-stranded structure contributes a single seam of (core) knobs-into-holes to the helical interface. 3-, 4-, and 5-Stranded structures, however, are best considered as rings of helices with cycles of knobs-into-holes. These higher-order oligomers make additional (peripheral) knobs-into-holes that broaden the helical contacts. Combinations of core and peripheral knobs may be assigned to different sequence repeats offset within the same helix. Such multiple repeats lead to multi-faceted helices, which explain structures above dimers. For instance, coiled-coil oligomer state correlates with the offset of the different repeats along a sequence. In addition, certain multi-helix assemblies can be considered as conjoined coiled coils in which multi-faceted helices participate in more than one coiled-coil motif.
authors.affiliation: Centre for Biomolecular Design and Drug Development, John Maynard-Smith Building, School of Life Sciences, University of Sussex, Falmer BN1 9QG, UK.
authors.forename: John
authors.initials: J
authors.lastname: Walshaw
authors.forename: Derek N
authors.initials: DN
authors.lastname: Woolfson
mesh_terms: D000465:Algorithms; D020816:Amino Acid Motifs; D008958:Models, Molecular; D009690:Nucleic Acid Conformation; D011485:Protein Binding; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D012984:Software