title: Preferred side-chain constellations at antiparallel coiled-coil interfaces.
abstract: Reliable predictive rules that relate protein sequence to structure would facilitate postgenome predictive biology and the engineering and de novo design of peptides and proteins. Through a combination of experiment and analysis of the protein data bank (PDB), we have deciphered and rationalized new rules for helix-helix interfaces of a common protein-folding and association motif, the antiparallel dimeric coiled coil. These interfaces are defined by a specific pattern of interactions among largely hydrophobic side chains often referred to as knobs-into-holes (KIH) packing: a knob from one helix inserts into a hole formed by four residues on the partner. Previous work has focused on lateral interactions within the KIH motif, for example, between an a position on one helix and a d' position on the other in an antiparallel coiled coil. We show that vertical interactions within the KIH motif, such as a'-a-a', are energetically important as well. The experimental and database analyses concur regarding preferred vertical combinations, which can be rationalized as leading to favorable side-chain interactions that we call constellations. The findings presented here highlight an unanticipated level of complexity in coiled-coil interactions, and our analysis of a few specific constellations illustrates a general, multipronged approach to addressing this complexity.
authors.affiliation: Department of Chemistry, University of Wisconsin, Madison, WI 53706, USA.
authors.forename: Erik B
authors.initials: EB
authors.lastname: Hadley
authors.forename: Oliver D
authors.initials: OD
authors.lastname: Testa
authors.forename: Derek N
authors.initials: DN
authors.lastname: Woolfson
authors.forename: Samuel H
authors.initials: SH
authors.lastname: Gellman
mesh_terms: D020816:Amino Acid Motifs; D030562:Databases, Protein; D019281:Dimerization; D004952:Esters / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D008956:Models, Chemical; D008958:Models, Molecular; D008968:Molecular Conformation; D010455:Peptides / Q000737:chemistry; D011487:Protein Conformation; D017510:Protein Folding; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000737:chemistry*; D013816:Thermodynamics
chemical_list: D004952:Esters; D010455:Peptides; D011506:Proteins