title: A designed protein with packing between left-handed and right-handed helices.
abstract: A common motif in protein structures is the assembly of alpha-helices. Natural alpha-helical assemblies, such as helical bundles and coiled coils, consist of multiple right-handed alpha-helices. Here we design a protein complex containing both left-handed and right-handed helices, with peptides of D- and L-amino acids, respectively. The two peptides, D-Acid and L-Base, feature hydrophobic heptad repeats and are designed to pack against each other in a "knobs-into-holes" manner. In solution, the peptides form a stable, helical heterotetramer with tight packing in the most solvent-protected core. This motif may be useful for designing protease-resistant, helical D-peptide ligands against biological protein targets.
authors.affiliation: Howard Hughes Medical Institute, Whitehead Institute for Biomedical Research, Department of Biology, Massachusetts Institute of Technology, Nine Cambridge Center, Cambridge, Massachusetts 02142, USA.
authors.forename: S K
authors.initials: SK
authors.lastname: Sia
authors.forename: P S
authors.initials: PS
authors.lastname: Kim
mesh_terms: D000595:Amino Acid Sequence; D000817:Anilino Naphthalenesulfonates / Q000737:chemistry; D001667:Binding, Competitive; D002942:Circular Dichroism; D003903:Deuterium; D005456:Fluorescent Dyes / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D008969:Molecular Sequence Data; D019906:Nuclear Magnetic Resonance, Biomolecular; D010452:Peptide Biosynthesis; D010455:Peptides / Q000737:chemistry*; D011485:Protein Binding; D011489:Protein Denaturation; D015202:Protein Engineering / Q000379:methods; D017433:Protein Structure, Secondary; D011522:Protons; D020449:Repetitive Sequences, Amino Acid; D014461:Ultracentrifugation; D014508:Urea
chemical_list: D000817:Anilino Naphthalenesulfonates; D005456:Fluorescent Dyes; D010455:Peptides; D011522:Protons; C027132:1-anilino-8-naphthalenesulfonate; D014508:Urea; D003903:Deuterium