A designed protein with packing between left-handed and right-handed helices |
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Authors: | Sia S K Kim P S |
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Institution: | Howard Hughes Medical Institute, Whitehead Institute for Biomedical Research, Department of Biology, Massachusetts Institute of Technology, Nine Cambridge Center, Cambridge, Massachusetts 02142, USA. |
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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. |
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