title: The extended left-handed helix: a simple nucleic acid-binding motif.
abstract: The poly-proline type II extended left-handed helical structure is well represented in proteins. In an effort to determine the helix's role in nucleic acid recognition and binding, a survey of 258 nucleic acid-binding protein structures from the Protein Data Bank was conducted. Results indicate that left-handed helices are commonly found at the nucleic acid interfacial regions. Three examples are used to illustrate the utility of this structural element as a recognition motif. The third K homology domain of NOVA-2, the Epstein-Barr nuclear antigen-1, and the Drosophila paired protein homeodomain all contain left-handed helices involved in nucleic acid interactions. In each structure, these helices were previously unidentified as left-handed helices by secondary structure algorithms but, rather, were identified as either having small amounts of hydrogen bond patterns to the rest of the protein or as being "unstructured." Proposed mechanisms for nucleic acid interactions by the extended left-handed helix include both nonspecific and specific recognition. The observed interactions indicate that this secondary structure utilizes an increase in protein backbone exposure for nucleic acid recognition. Both main-chain and side-chain atoms are involved in specific and nonspecific hydrogen bonding to nucleobases or sugar-phosphates, respectively. Our results emphasize the need to classify the left-handed helix as a viable nucleic acid recognition and binding motif, similar to previously identified motifs such as the helix-turn-helix, zinc fingers, leucine zippers, and others.
authors.affiliation: Department of Biochemistry and Biophysics, Oregon State University, Corvallis 97331, USA.
authors.forename: Joshua M
authors.initials: JM
authors.lastname: Hicks
authors.forename: Victor L
authors.initials: VL
authors.lastname: Hsu
mesh_terms: D000465:Algorithms; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D017124:Conserved Sequence; D030562:Databases, Protein; D029721:Drosophila Proteins; D004331:Drosophila melanogaster; D019309:Epstein-Barr Virus Nuclear Antigens / Q000737:chemistry / Q000378:metabolism; D018398:Homeodomain Proteins / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D006860:Hydrogen Bonding; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000378:metabolism; D000090682:Neuro-Oncological Ventral Antigen; D009696:Nucleic Acids / Q000378:metabolism*; D010455:Peptides / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism
chemical_list: D029721:Drosophila Proteins; D019309:Epstein-Barr Virus Nuclear Antigens; D018398:Homeodomain Proteins; C406163:NOVA2 protein, human; D009419:Nerve Tissue Proteins; D000090682:Neuro-Oncological Ventral Antigen; D009696:Nucleic Acids; C082157:PRRX1 protein, human; D010455:Peptides; D011506:Proteins; D016601:RNA-Binding Proteins; C489935:prd protein, Drosophila; C011083:polyproline; C417029:EBV-encoded nuclear antigen 1